PRODUCTS

ORTHO PHTHALALDEHYDE

Phthalaldehyde (sometimes also o-phthalaldehyde or ortho-phthalaldehyde, Ortho phthalaldehyde) is the chemical compound with the formula C6H4(CHO)2. It is one of three isomers of benzene dicarbaldehyde, related to phthalic acid. This pale yellow solid is a building block in the synthesis of heterocyclic compounds and a reagent in the analysis of amino acids. Ortho phthalaldehyde dissolves in water solution at pH < 11.5. Its solutions degrade upon UV illumination and exposure to air.

CAS No. : 643-79-8
EC No. : 211-402-2

Synonyms:
Ortho-phthalaldehyde; OPA; Benzene-1,2-dicarboxaldehyde; o-Phthalaldehyde; o-Phthalic dicarboxaldehyde; Phthaldialdehyde; Phthalaldehyde; Benzene-1,2-dicarbaldehyde; o-Phthalaldehyde; 643-79-8; PHTHALALDEHYDE; o-Phthaldialdehyde; 1,2-Benzenedicarboxaldehyde; Benzene-1,2-dicarboxaldehyde; Phthaldialdehyde; Phthalic aldehyde; Phthalic dialdehyde; ortho-Phthalaldehyde; Phthalyldicarboxaldehyde; Phthalic dicarboxaldehyde; o-Phthaldehyde; benzene-1,2-dicarbaldehyde; Phthalaldialdehyde; o-Phthalicdicarboxaldehyde; 1,2-Diformylbenzene; 2-PHTHALALDEHYDE; 1,2-Phthalic dicarboxaldehyde; ortho Phthalaldehyde; o-Phthalic dicarboxaldehyde; 1,2-BENZENEDICARBALDEHYDE; OPA; OPTA; Phtalaldehydes [French]; NSC 13394; UNII-4P8QP9768A; CHEBI:70851; 2-PHTHALDIALDEHYDE; EINECS 211-402-2; ORTHO PHTHALALDEHYDE; Ortho Phthalaldehyde; Phtalaldehydes; 1,2-Phthalic dicarboxaldehyde, 98+%; CAS-643-79-8; Orthophthaldialdehyde; ortho-Phthalic Aldehyde; phthalaldehyd; o-Phthalaldehyd; o-phthal aldehyde; orthophthalaldehyde; Phtharal (JAN); Disopa (TN); 2-PHTHALDEHYDE; Phthaldialdehyde Reagent; PubChem17402; ORTHO-PHTHALADEHYDE; Epitope ID:176774; O-PHTHALIC DIALDEHYDE; 2-Phthaldehyde, High purity; SCHEMBL33393; Benzene-1,2-dicarboxakdehyde; 4-07-00-02138 (Beilstein Handbook Reference); 1,2-Phthalic dicarboxyaldehyde; Ortho-phthalaldehyde; OPA; Benzene-1,2-dicarboxaldehyde; o-Phthalaldehyde; o-Phthalic dicarboxaldehyde; Phthaldialdehyde; Phthalaldehyde; Benzene-1,2-dicarbaldehyde; o-Phthalaldehyde; 643-79-8; PHTHALALDEHYDE; o-Phthaldialdehyde; 1,2-Benzenedicarboxaldehyde; Benzene-1,2-dicarboxaldehyde; Phthaldialdehyde; Phthalic aldehyde; Phthalic dialdehyde; ortho-Phthalaldehyde; Phthalyldicarboxaldehyde; Phthalic dicarboxaldehyde; o-Phthaldehyde; benzene-1,2-dicarbaldehyde; Phthalaldialdehyde; Ortho-Phthalic Aldehyde (OPA); BENZENE-1,2-DIALDEHYDE; 1,2-Benzenedialdehyde;Phthalaldehyde; FLUORALDEHYDE(TM) O-PHTHALALDEHYDE; ORTHO PHTHALALDEHYDE; Ortho Phthalaldehyde; Benzene-1,2-dicarboxaldehyde 643-79-8; Phthaldialdehyde Reagent, Solution Complete; Phthaldialdehyde Reagent, Solution Incomplete; Phthaldialdehyde, for fluorescence, >=99.0% (HPLC); 6-Oxomethylene-5-[(E)-hydroxymethylene]cyclohexa-1,3-diene; 6-Oxomethylene-5-[(Z)-hydroxymethylene]cyclohexa-1,3-diene; Phthaldialdehyde, >=97% (HPLC), powder (may contain lumps); Phthaldialdehyde, suitable for HPLC fluorimetric detection of amino acids, >=99% (HPLC), powder

Ortho Phthalaldehyde

Ortho phthalaldehyde: a possible alternative to glutaraldehyde for high level disinfection

Ortho phthalaldehyde (OPA) was tested against a range of organisms including glutaraldehyde-resistant mycobacteria, Bacillus subtilis spores and coat-defective spores. Glutaraldehyde (GTA) and peracetic acid (PAA) were tested for comparative purposes. Both suspension and carrier tests were performed using a range of concentrations and exposure times. All three biocides were very effective (> or = 5 log reduction) against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa in suspension tests. Ortho phthalaldehyde and GTA (PAA was not tested) were also very effective against Staph. aureus and Ps. aeruginosa in carrier tests. Ortho phthalaldehyde showed good activity against the mycobacteria tested including the two GTA-resistant strains, but 0.5% w/v Ortho phthalaldehyde was found not to be sporicidal. However, limited activity was found with higher concentrations and pH values. Coat-defective spores were more susceptible to Ortho phthalaldehyde, suggesting that the coat may be responsible for this resistance. The findings of this study suggest that Ortho phthalaldehyde is effective against GTA-resistant mycobacteria and that it is a viable alternative to GTA for high level disinfection.

USES of Ortho Phthalaldehyde
A reagent that forms fluorescent conjugation products with primary amines. It is used for the detection of many biogenic amines, peptides, and proteins in nanogram quantities in body fluids.

Synthesis and reactions
The compound was first described in 1887 when it was prepared from α,α,α’,α’-tetrachloro-ortho-xylene.[4] A more modern synthesis is similar: the hydrolysis of the related tetrabromo-o-xylene using potassium oxalate, followed by purification by steam distillation.[2]

The reactivity of Ortho phthalaldehyde is complicated by the fact that in water it forms both a mono- and dihydrate, C6H4(CHO)(CH(OH)2) and C6H4(CH(OH))2O, respectively. Its reactions with nucleophiles often involves the reaction of both carbonyl groups.[5]

Orthophthalaldehyde and hydrated forms 001.png
Biochemistry
Ortho phthalaldehyde is used in a very sensitive fluorescent reagent for assaying amines or sulfhydryls in solution, notably contained in proteins, peptides, and amino acids, by capillary electrophoresis and chromatography. Ortho phthalaldehyde reacts specifically with primary amines above their isoelectric point Pi in presence of thiols. Ortho phthalaldehyde reacts also with thiols in presence of an amine such as n-propylamine or 2-aminoethanol. The method is spectrometric (fluorescent emission at 436-475 nm (max 455 nm) with excitation at 330-390 nm (max. 340 nm)).[6]

Disinfection
Ortho phthalaldehyde is commonly used as a high-level disinfectant for medical instruments, commonly sold under the brand names of Cidex Ortho phthalaldehyde or TD-8. Disinfection with Ortho phthalaldehyde is indicated for semi-critical instruments that come into contact with mucous membranes or broken skin, such as specula, laryngeal mirrors, and internal ultrasound probes.

Poly(phthalaldehyde)
Ortho phthalaldehyde can be polymerized. In the polymer, one of the oxygen atoms forms a bridge to the other non-ring carbon of the same phthalaldehyde unit, while the other bridges to a non-ring carbon of another phthalaldehyde unit. Poly(phthalaldehyde) is used in making a photoresist.

In winemaking
The Nitrogen by O-Phthaldialdehyde Assay (NOrtho phthalaldehyde) is one of the methods used in winemaking to measure yeast assimilable nitrogen (or YAN) needed by wine yeast in order to successfully complete fermentation.[9]

Isomeric phthalaldehydes
Related to phthalaldehyde are:
isophthalaldehyde (benzene-1,3-dicarbaldehyde; m.p. 87–88 °C, CAS# 626-19-7)
terephthalaldehyde (benzene-1,4-dicarbaldehyde; m.p. 114–116 °C, CAS# 623-27-8)

Properties
Chemical formula C8H6O2
Molar mass 134.134 g·mol−1
Appearance Yellow solid
Density 1.19 g/mL
Melting point 55.5 to 56 °C (131.9 to 132.8 °F; 328.6 to 329.1 K)[2]
Boiling point 266.1 °C (511.0 °F; 539.2 K)
Solubility in water Low

Ortho Phthalaldehyde is a known environmental transformation product of Dithianon.

Ortho phthalaldehyde is mainly used as a high-level disinfectant (a low-temperature chemical method) for heat-sensitive medical and dental equipment such as endoscopes and thermometers; in recent years, it has gained popularity as a safe and better alternative to glutaraldehyde.
There are some researches show, pH7.5 contains the sterilizing agent of Ortho phthalaldehyde 0.5%, and its sterilizing power, sterilization speed, stability and toxicity all are better than glutaraldehyde, can kill mycobacterium in the 5min, the bacterium number reduces by 5 logarithmic value, and Ortho phthalaldehyde is very stable, tasteless in pH3～9 scopes, non-stimulated to human nose, eye mucosa, and need not activate before using, various materials are had good consistency, have tangible microbiocidal activity.

USES of Ortho phthalaldehyde
Ortho phthalaldehyde can be widely used for precolumn derivatization of amino acids in HPLC separation or Capillary electrophoresis. For flow cytometric measurements of protein thiol groups.

Uses
Ortho phthalaldehyde can be used for precolumn derivatization of amino acids for HPLC separation and for flow cytometric measurements of protein thiol groups.

Uses
Precolumn derivatization reagent for primary amines and amino acids. The fluorescent derivative can be detected by reverse-phase HPLC. The reaction requires OPA, primary amine and a sulfhydryl. In the presence of excess sulfhydryl, amines can be quantitated. In the presence of excess amine, sulfhydryls can be quantitated.

Uses
Disinfectant. Reagent in fluorometric determination of primary amines and thiols.

Preparation
Ortho phthalaldehyde is a high-level chemical disinfectant that is commonly used for disinfection of dental and medical instruments as an alternative to glutaraldehyde, which is a known skin and respiratory sensitizer.
A variety of processes for manufacturing Ortho phthalaldehyde have been reported in the literature.
Ortho phthalaldehyde is produced by heating pure benzaldehyde and chloroform with potassium hydroxide solution. The resulting solution is further acidified with hydrochloric acid and cooled to yield a colorless powder of Ortho phthalaldehyde.
It is also produced by ozonization of naphthalene in alcohol followed by catalytic hydrogenation.
Catalytic oxidation of various chemicals is also used in manufacturing Ortho phthalaldehyde. Ortho phthalaldehyde can be manufactured by oxidation of phthalan by nitrogen monoxide in acetonitrile with N-hydroxyphthalimide as the catalyst to yield 80% to 90%.

Ortho phthalaldehyde is a pale, yellow crystal or colorless powder. It is soluble in water. USE: Ortho phthalaldehyde is used as a disinfectant, mainly for dental and medical equipment. EXPOSURE: Workers that produce or use Ortho phthalaldehyde may have direct skin contact. The general population may be exposed by contact with residual disinfectant. If Ortho phthalaldehyde is released to the environment, it will be broken down in air by reaction with hydroxyl radicals. It may be broken down in the air by sunlight. It will not volatilize into air from soil or water surfaces. It is expected to move easily through soil. It is not expected to build up in fish. RISK: Irritation to the skin, eyes, and respiratory tract as well as asthma and allergic skin rashes have been reported in some healthcare workers that routinely use Ortho phthalaldehyde to disinfect equipment. Severe anaphylactic allergic reactions have been reported in some patients exposed to equipment disinfected with Ortho phthalaldehyde. Discoloration of the mouth and throat, burning of the throat, nausea, vomiting, and diarrhea may occur with ingestion. Damage to the nose, throat, lung, skin, and eyes were observed in laboratory animals following repeated exposure to low air levels of Ortho phthalaldehyde, damage was severe at moderate air levels and some animals died. Several alterations in the blood were also observed. Damage to the gastrointestinal tract, irregular breathing, impaired movement, and changes in the blood were observed in laboratory animals given moderate oral doses. Some animals died at high oral doses. No evidence of abortion or birth defects were noted in laboratory animals exposed to Ortho phthalaldehyde during pregnancy, but delayed bone development was observed at high doses that made the mothers sick. Data on the potential for Ortho phthalaldehyde to cause infertility in laboratory animals were not available. However, damage to the testis and reduced sperm counts and motility were observed in male animals following repeated exposure to low air levels of Ortho phthalaldehyde. Data on the potential for Ortho phthalaldehyde to cause cancer in laboratory animals were not available. The potential for Ortho phthalaldehyde to cause cancer in humans has not been assessed by the U.S. EPA IRIS program, the International Agency for Research on Cancer, or the U.S. National Toxicology Program 14th Report on Carcinogens.

For Ortho phthalaldehyde (USEPA/OPP Pesticide Code: 129017) there are 0 labels match. /SRP: Not registered for current use in the USA, but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses.

Recently, the use of ortho phthalaldehyde (OPA) has been increasing as an alternative to glutaraldehyde(GA)for endoscope disinfection. We detected development of bronchial asthma and contact dermatitis in health care workers (HCW) employed in an endoscopy unit. ... Two of 83 health care workers described mild eye irritation, but no contact dermatitis or bronchitis had newly developed.

Three sampling and analytical methods have been developed and evaluated for Ortho phthalaldehyde (OPA): (1) an HPLC-UV method for Ortho phthalaldehyde in air, (2) a fluorimetric method for Ortho phthalaldehyde on surfaces, and (3) a colorimetric method for Ortho phthalaldehyde on surfaces. (1) The air sampler contains 350 mg of silica gel coated with 1 mg of acidified 2,4-dinitrophenylhydrazine (DNPH). Air sampling may be conducted at 0.03 to 1.0 L/min for periods up to 8 hr. Samples were eluted with ethyl acetate, and the eluents were allowed to stand for 72 hr. Analysis was by high performance liquid chromatography (HPLC) with a UV detector set at 369 nm. An unusual phenomenon was the observation that the stability of the sample on a sampler at 3 degrees C tends to decrease as the total quantity of Ortho phthalaldehyde collected on the sampler decreases. Elution of the samples within 24 hr of air sampling is required. The detection limit (LOD) is approximately 0.02 ug of Ortho phthalaldehyde per sample. Ortho phthalaldehyde on surfaces may be collected with strips cut from a sheet of polyvinyl alcohol (PVA wipe). (2) In the surface wipe method with analysis by fluorescence measurement, the strips of PVA wipe were placed into dimethyl sulfoxide. An aliquot was treated with aqueous N-acetyl-l-cysteine and ethylenediamine. Analysis was performed with a portable fluorometer (excitation and emission wavelengths = 365 nm and 438 nm, respectively). The LOD is 0.2 ug per sample. (3) In the surface wipe method with visual colorimetric detection, the strips of PVA wipe were placed into 30:70 acetonitrile:water. An aliquot was treated with N-(1-naphthyl)ethylenediamine in 0.1 m sulfuric acid. After color development, the LOD is approximately 48 ug per sample. These methods have been field tested in a hospital.

A simple high performance liquid chromatographic (HPLC) method and a highly sensitive gas chromatography mass spectrometric (GC-MS) method have been established for the determination of Ortho phthalaldehyde (OPA) in water. These methods are based on the derivatization of Ortho phthalaldehyde with hydrazine in water. The following optimum reaction conditions were established: reagent dosage, 20 mg/mL of hydrazine; pH 2; reaction for 20 min at 70 °C. The organic derivative was detected directly by HPLC or after the extraction with methylene chloride/concentration by GC-MS. The limit of detection of Ortho phthalaldehyde in water was 4.0 and 0.3 ug/L by HPLC and GC-MS, respectively. The calibration curve showed good linearity with r2 = 0.9993 and r2 = 0.9994 by HPLC and GC-MS, respectively, the accuracy was in a range of 95-105%, and the precision of the assay was less than 13% in water. The HPLC method was simple and reproducible enough to permit the Ortho phthalaldehyde content analysis in the disinfectant products, and the GC-MS method is sensitive enough to permit reliable analysis of Ortho phthalaldehyde to the ug/L level in environmental water.

2018 Notice of Intended Changes (NIC): These substances, with their corresponding values and notations, comprise those for which (1) a limit is proposed for the first time, (2) a change in the Adopted value is proposed, (3) retention as an NIC is proposed, or (4) withdrawal of the Documentation and adopted TLV is proposed. In each case, the proposals should be considered trial values during the period they are on the NIC. These proposals were ratified by the ACGIH Board of Directors and will remain on the NIC for approximately one year following this ratification. If the Committee neither finds nor receives any substantive data that changes its scientific opinion regarding an NIC TLV, the Committee may then approve its recommendation to the ACGIH Board of Directors for adoption. If the Committee finds or receives substantive data that change its scientific opinion regarding an NIC TLV, the Committee may change its recommendation to the ACGIH Board of Directors for the matter to be either retained on or withdrawn from the NIC. Substance: Ortho Phthalaldehyde; Time Weighted Avg (TWA): Surface Limit 0.025 mg/100 sq cm; Short Term Exposure Limit (STEL): Ceiling 0.0001 ppm (vapor fraction); Notations: Skin, Dermal Sensitization, Respiratory Sensitization; Molecular Weight: 134.10; TLV Basis: Eye, skin & respiratory tract irritation; respiratory sensitization; anaphylaxis.

IDENTIFICATION AND USE: Ortho Phthalaldehyde (Ortho phthalaldehyde) is used as disinfectant and reagent in fluorometric determination of primary amines and thiols. HUMAN STUDIES: Ortho phthalaldehyde is a commonly used solution for rapid sterilization of medical equipment. Cases of anaphylaxis following cystoscopy with endoscopes sterilized with this agent have been reported. Ortho phthalaldehyde-induced anaphylaxis following laryngoscopy have also been described. In these patients, Ortho phthalaldehyde-specific IgE was detected in the serum. Contact dermatitis occurred in 4 workers of the endoscopy unit, one of whom also developed asthma. Among 80 female disinfection workers who used only antiseptic solutions containing Ortho phthalaldehyde, the incidence of disinfection-related complaints were 10% skin, 9% eye, and 16% respiratory symptoms. ANIMAL STUDIES: In male mice, injected Ortho phthalaldehyde induced specific IgE and IgG in the sera, suggesting that Ortho phthalaldehyde acts as a hapten. Overall, Ortho phthalaldehyde caused acute inflammation and acted as a haptenic allergen, although it caused only mild liver injury. In mice sensitized to ovalbumin (OVA), Ortho phthalaldehyde enhanced the OVA-induced recruitment of neutrophils to the lung and the production of allergen-specific IgE, suggesting that Ortho phthalaldehyde acts as an immunological adjuvant. The major targets from Ortho phthalaldehyde exposure in rats and mice included the respiratory system (nasal cavity, larynx, trachea, and lung), skin, eye, testis, and epididymis. The most sensitive measure of Ortho phthalaldehyde inhalation toxicity in male and female rats and mice was significantly increased incidences of nasal cavity lesions (lowest-observable-effect concentration = 0.44 ppm). Ortho phthalaldehyde was mutagenic in Salmonella typhimurium strain TA100 in the absence of exogenous metabolic activation; no mutagenicity was seen in TA100 with metabolic activation or in TA98 or Escherichia coli WP2 uvrA/pKM101, with or without metabolic activation.

Iatrogenic injury from medical disinfectants is an uncommon but potentially devastating complication. We report an unusual, but severe, upper aerodigestive complication from the use of Ortho phthalaldehyde solution, a commonly used endoscope disinfectant.

Ortho phthalaldehyde (Cidex Ortho phthalaldehyde) is a commonly used solution for rapid sterilization of flexible endoscopic equipment. We report two cases of anaphylaxis following cystoscopy with endoscopes sterilized with this agent. Only a handful of such reactions have been reported in the published literature, the majority of which are in the bladder cancer population undergoing surveillance cystoscopy. PATIENTS AND METHODS: We reviewed the clinical presentation of two cases of anaphylaxis following flexible cystoscopy with instruments sterilized with Ortho phthalaldehyde. We further describe their subsequent evaluation by an allergy and immunology specialist who performed skin testing to confirm a suspected Ortho phthalaldehyde allergy. RESULTS: Both patients were skin test positive to Ortho phthalaldehyde antigen. As a result, sterilization techniques for our flexible endoscopes has been altered. To date, no further anaphylactic reactions have occurred in our bladder cancer patients, including the two cases presented herein following subsequent cystoscopic evaluations. CONCLUSIONS: Ortho phthalaldehyde-sterilized cystoscopes have been associated with anaphylactic reactions in a small number of patients who have undergone repeated cystoscopy. The manufacturer has already made recommendations to avoid this agent in bladder cancer patients. It may be prudent to extend this practice to other populations undergoing repeat cystoscopy.

Ortho phthalaldehyde (OPA) has recently been used as a disinfectant for various medical apparatuses. Ortho phthalaldehyde is not generally recognized as a potential allergen. CASE SUMMARY: Subsequent to our recent report describing a patient presenting with Ortho phthalaldehyde-induced anaphylaxis following laryngoscopy, we experienced two more such cases. In all three cases, the basophil histamine release test was useful for identifying the allergen as Ortho phthalaldehyde. Ortho phthalaldehyde-specific IgE was successfully detected in the serum of the patients by ELISA. DISCUSSION: Physicians and co-medical workers need to be aware of potential allergens to which patients may be exposed during routine medical procedures.

Because body fluids and blood have a tendency to adhere to transesophageal echo devices, a high level of sterilization is required when cleaning them. Ortho phthalaldehyde (OPA) has been widely used in Japan since being approved as a high-level sterilant. The authors report a patient with widespread, severe skin and mucous membrane damage of the lip, tongue, pharynx and esophagus areas that was attributed to inadequate washing after the sterilization of a transesophageal echo device with Ortho phthalaldehyde. This patient experienced sequelae, which did not improve after more than 1 year of continuous treatment. When using medical devices sterilized with Ortho phthalaldehyde, the use of a probe cover, when applicable, is recommended and complete washing prior to use is required.

Acute Exposure/ Although Ortho phthalaldehyde (OPA) has been suggested as an alternative to glutaraldehyde for the sterilization and disinfection of hospital equipment, the toxicity has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of Ortho phthalaldehyde. The EpiDerm Skin Irritation Test was used to evaluate in vitro irritancy potential of Ortho phthalaldehyde and glutaraldehyde. Treatment with 0.4125 and 0.55% Ortho phthalaldehyde induced irritation, while glutaraldehyde exposure at these concentrations did not. Consistent with the in vitro results, Ortho phthalaldehyde induced irritancy, evaluated by ear swelling, when mice were treated with 0.75%. Initial evaluation of the sensitization potential was conducted using the local lymph node assay at concentrations ranging from 0.005 to 0.75%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.051% compared to that of 0.089%, previously determined for glutaraldehyde. Immunoglobulin (Ig) E-inducing potential was evaluated by phenotypic analysis of draining lymph node (DLN) cells and measurement of total and specific serum IgE levels. The 0.1 and 0.75% exposed groups yielded significant increases in the IgE+B220+ cell population in the lymph nodes while the 0.75% treated group demonstrated significant increases in total IgE, Ortho phthalaldehyde-specific IgE, and Ortho phthalaldehyde-specific IgG(1). In addition, significant increases in interleukin-4 messenger RNA and protein expression in the DLNs were observed in Ortho phthalaldehyde-treated groups. The results demonstrate the dermal irritancy and allergic potential of Ortho phthalaldehyde and raise concern about the proposed/intended use of Ortho phthalaldehyde as a safe alternative to glutaraldehyde.

Acute Exposure/ Ortho phthalaldehyde (OPA) has been used as a safe alternative disinfectant instead of glutaraldehyde; however, recently some adverse effects of Ortho phthalaldehyde were reported in patients and medical professions. We examined the acute toxicity of Ortho phthalaldehyde in male ICR mice injected with 0.125-0.5% Ortho phthalaldehyde and killed some animals 1 day after a single Ortho phthalaldehyde injection, and others 1 or 13 days after two Ortho phthalaldehyde injections 5 days apart. Hematology, blood cell counts, specific antibody production, organ weights, hepatic enzymes, hepatic histOrtho phthalaldehydethology and gene expression of cytochrome P450 (CYP) mRNA in liver were examined. Single Ortho phthalaldehyde injections elevated leukocyte counts, the proportion of neutrophils, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Two Ortho phthalaldehyde injections dose-dependently increased leukocyte counts, the proportion of neutrophils, ALT and AST, and decreased alkaline phosphatase. Leukocyte counts and proportions of neutrophils normalized 13 days after the second of two injections. However, both ALT and AST remained high in mice given higher Ortho phthalaldehyde doses. Significant increased liver-to-body weight ratio and mild hepatic lesions were observed. Gene expression of CYP1a1 and CYP2e1 revealed a tendency of up-regulation 1 day after two Ortho phthalaldehyde injections. However, expression of these genes was then down-regulated 13 days after Ortho phthalaldehyde injections. Ortho phthalaldehyde induced specific IgE and IgG significantly in the sera, suggesting that Ortho phthalaldehyde acts as a hapten. Overall, Ortho phthalaldehyde caused acute inflammation and acted as a haptenic allergen, although it caused only mild liver injury. Such evidence suggested that careful washing and prevention of exposure were needed after Ortho phthalaldehyde disinfection of medical instruments.

Developmental or Reproductive Toxicity/ The general population is exposed to phthalates through consumer products, diet, and medical devices. Phthalic acid (PA) is a common final metabolite of phthalates, and its isomers include isophthalic acid (IPA), terephthalic acid (TPA), and phthalaldehyde (o-phthalic acid, Ortho phthalaldehyde). The purpose of this study was to investigate whether PA and PA isomers exert reproductive toxicity, including altered sperm movement. In vitro cell viability assays were comparatively performed using Sertoli and liver cell lines. In animal experiments, PA or PA isomers (10, 100, or 1000 mg/kg) were administered orally to Sprague-Dawley (SD) rats, and semen samples were analyzed by computer-aided sperm analysis (CASA). PA treatment produced a significant effect on curvilinear velocity (VCL), straight-line velocity (VSL), mean velocity or average path velocity (VAP), amplitude of lateral head displacement (ALH), and frequency of head displacement or beat cross-frequency (BCF), whereas IPA, TPA, and Ortho phthalaldehyde induced no marked effects. In vitro cell viability assays showed that mouse normal testis cells (TM4) and human testis cancer cells (NTERA 2 cl. D1) were more sensitive to PA and Ortho phthalaldehyde than mouse liver normal cells (NCTC clone 1469) and human fetal liver cells (FL 62891). Our study suggests that PA and PA isomers specifically produced significant in vitro and in vivo reproductive toxicity, particularly sperm toxicity and testis cell cytotoxicity. Of the isomers examined, PA appeared to be the most toxic and may serve as a surrogate biomarker for reproductive toxicity following mixed exposure to phthalates.

Neurotoxicity/ Glutaraldehyde (GA) and ortho-phtalaldehyde (Ortho phthalaldehyde) have been widely used as major components of disinfectants in hospitals. We evaluated the alterations in GA or Ortho phthalaldehyde in rats after subacute inhalation exposure by determining levels of neurotransmitters (norepinephrine [NE], dOrtho phthalaldehydemine [DA], DA metabolites, dihydroxyphenylacetic acid [DOrtho phthalaldehydeC] and homovanillic acid [HVA], indoleamine serotonin [5-HT] and 5-HT metabolite, 5-hydroxyindoleacetic acid [5-HIAA]) in discrete brain regions using high performance liquid chromatography (HPLC) equipped with an electrochemical detector. Female Wistar rats were exposed to 0, 50, 100, or 200 ppb gaseous GA or Ortho phthalaldehyde by inhalation for 1 hr per day, 5 d per week for 4 wk. Following the exposure, the brain of each rat was removed and dissected into cerebrum, cerebellum, medulla oblongata, midbrain, corpus striatum and hypothalamus. The neurotransmitters and their metabolites were extracted from each brain region, and determined by HPLC. Regarding GA, the daily water intake of the 50 or the 200 ppb exposed groups was significantly lower than that of the control. DA and 5-HIAA levels in the medulla oblongata among the GA exposed groups were significantly lower than those of the control. For Ortho phthalaldehyde, the mean final body weight and daily food intake of the 100 or 200 ppb exposed groups were significantly lower than those of the control. The mean DA concentrations in the cerebrum in the groups exposed to Ortho phthalaldehyde were significantly lower than those of the control. Ortho phthalaldehyde may modulate DA metabolism in the cerebrum of female rats. The levels GA or Ortho phthalaldehyde that induced alienations in neurotransmitters were comparable to those levels usually found in hospitals, further studies are warranted to evaluate the of safety of disinfectants containing GA or Ortho phthalaldehyde.

Groups of 10 male and 10 female rats and mice were exposed to Ortho Phthalaldehyde at concentrations of 0, 0.44, 0.88, 1.75, 3.5, or 7.0 ppm, 6 hours plus T90 (17 minutes) per day, 5 days per week for 14 weeks; additional groups of 10 male and 10 female clinical pathology study rats were exposed to the same concentrations for 23 days. All rats exposed to 7.0 ppm died by the end of week 2 of the study, and seven males and two females exposed to 3.5 ppm died by week 7 of the study. All mice exposed to 7.0 ppm died during week 1 of the study, and five males and four females exposed to 3.5 ppm died by week 6 of the study. Clinical observations in rats and mice included abnormal breathing, sneezing, and thinness, with increasing frequency in higher exposure groups. In rats, clinical observations also included black discoloration of the appendages (pinnae and/or feet), which was noted throughout the study in male and female rats exposed to 3.5 ppm or greater. Clinical observations in mice also included alopecia. Mean body weights of all surviving exposed groups of male rats and 1.75 and 3.5 ppm female rats were significantly less than those of the chamber controls. Mean body weights of all surviving exposed groups of male and female mice were significantly less than those of the chamber controls, and 3.5 ppm males lost weight during the study. In the hematopoietic system of rats, decreases in lymphocyte counts in males and females coincided with increases in neutrophil counts. These alterations in lymphocyte and neutrophil counts were consistent with stress and inflammation. Decreased lymphocyte counts corresponded to lymphoid atrophy in the thymus and spleen. Within the erythron, the erythrocyte counts, hemoglobin concentrations, hematocrit values, and packed cell volumes were significantly elevated in both male and female rats at all time points. Erythron increases at the earlier time points were consistent with a physiological hemoconcentration, while increases at study termination may have been due to hypoxia with a resultant secondary erythrocytosis. In the hematopoietic system of mice, the total leukocyte and lymphocyte counts, as well as neutrophil and eosinophil counts, were increased in males at study termination.

Similarly, female mice had increased total leukocyte, neutrophil, and eosinophil counts. The increases in the leukon were generally consistent with inflammation. Hemoglobin concentrations, erythrocyte counts, hematocrit values, and packed cell volumes were decreased in male and female mice. The decreases in the erythron were most likely due to bone marrow suppression as a result of the chronic inflammation in the respiratory tract. Inhalation exposure to Ortho Phthalaldehyde resulted in a spectrum of lesions at sites of contact within the respiratory tract (nose, larynx, trachea, and lung), skin, and eye that were generally consistent with an irritant effect. In general, exposure of rats and mice to Ortho Phthalaldehyde resulted in lesions throughout the respiratory tract that included necrosis, inflammation, regeneration, hyperplasia, and metaplasia, ranging from minimal to moderate in severity. In general, histologic findings occurred at deeper sites within the respiratory tract with increasing exposure concentration. The first site of contact, the nose, was most affected, with many lesions occurring at the lowest exposure concentration (0.44 ppm) in male and female rats and mice. Laryngeal lesions occurred at all exposure concentrations in rats and at 0.88 ppm or greater in mice. Tracheal findings were first noted at a variety of exposure concentrations. Lung findings were most prevalent at the two highest exposure concentrations (3.5 and 7.0 ppm) in rats and mice. In the skin, there were significant increases in adnexa degeneration and epithelial parakeratosis in both male and female rats and mice. In the eye, there were significant increases in suppurative inflammation of the anterior chamber and cornea, as well as corneal necrosis in male and female rats. Rats exposed to Ortho Phthalaldehyde exhibited lower cauda epididymis, epididymis, and testis weights. In rats, total sperm/cauda exhibited a negative trend and sperm motility was lower.

There were no histOrtho phthalaldehydethologic correlates identified that could explain the observed responses in sperm parameters, or the weight changes in the testis or epididymis. However, in the higher dose groups where morbidity and mortality were observed, testicular and epididymal histOrtho phthalaldehydethologic lesions were noted. In the testes, these lesions included significant increases in the incidences of elongated spermatid degeneration, apoptosis of the germinal epithelium, and interstitial cell atrophy. In the epididymis of male rats, there were significant increases in the incidences of exfoliated germ cells and apoptosis of the epithelium. The mice also displayed decreased sperm motility, and some testicular and epididymal histOrtho phthalaldehydethologic lesions, including significantly increased incidences of exfoliated germ cells of the epididymal duct, as well as multifocal cellular depletion of the germinal epithelium, and interstitial cell atrophy of the testis. Ortho Phthalaldehyde was mutagenic in Salmonella typhimurium strain TA100 in the absence of exogenous metabolic activation (S9 mix); no mutagenicity was seen in TA100 with S9 or in TA98 or Escherichia coli WP2 uvrA/pKM101, with or without S9. Following 3 months of inhalation exposure to Ortho Phthalaldehyde, no increases in the frequencies of micronucleated reticulocytes were observed in male or female Sprague Dawley rats. In B6C3F1/N mice following 3 months of inhalation exposure to Ortho Phthalaldehyde, a small increase in micronucleated reticulocytes was seen in male mice exposed to 3.5 ppm, but no significant increases in micronuclei were seen in erythrocytes of male mice or in reticulocytes or erythrocytes of female mice. A small increase in the percentage of reticulocytes was seen in female mice at the highest dose tested (3.5 ppm). Under the conditions of these 3-month inhalation studies, there were treatment-related lesions in male and female rats and mice. The major targets from Ortho Phthalaldehyde exposure in rats and mice included the respiratory system (nasal cavity, larynx, trachea, and lung), skin, eye, testis, and epididymis. The most sensitive measure of Ortho Phthalaldehyde inhalation toxicity in male and female rats and mice was significantly increased incidences of nasal cavity lesions (lowest-observable-effect concentration = 0.44 ppm). A no-observed-effect concentration was not reached in rats or mice of either sex.

Ortho Phthalaldehyde's production and use as a disinfectant may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 5.2X10-3 mm Hg at 21 °C indicates Ortho Phthalaldehyde will exist solely as a vapor in the atmosphere. Vapor-phase Ortho Phthalaldehyde will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 17 hours. Ortho Phthalaldehyde has an absorption peak at 297 nm and, therefore, may be susceptible to direct photolysis by sunlight. If released to soil, Ortho Phthalaldehyde is expected to have very high mobility based upon an estimated Koc of 10. Volatilization from moist soil surfaces is not expected based upon an estimated Henry's Law constant of 1.8X10-8 atm-cu m/mole. Ortho Phthalaldehyde is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation data in soil or water were not available. If released into water, Ortho Phthalaldehyde is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to Ortho Phthalaldehyde may occur through dermal contact with this compound at workplaces where Ortho Phthalaldehyde is produced or used. Monitoring and use data indicate that the general population may be exposed to Ortho Phthalaldehyde via contact with products containing residual disinfectant.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that Ortho Phthalaldehyde is expected to have very high mobility in soil(SRC). Volatilization of Ortho Phthalaldehyde from moist soil surfaces is not expected(SRC) given an estimated Henry's Law constant of 1.8X10-8 atm-cu m/mole(SRC) based upon its vapor pressure, 5.2X10-3 mm Hg(3), and water solubility, 5.0X10+4 mg/L(3). Ortho Phthalaldehyde is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). Biodegradation data in soil were not available(SRC, 2018).

Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that Ortho Phthalaldehyde is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.8X10-8 atm-cu m/mole(SRC), derived from its vapor pressure, 5.2X10-3 mm Hg(4), and water solubility, 5.0X10+4 mg/L(4). Ortho Phthalaldehyde is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). According to a classification scheme(5), an estimated BCF of 3(SRC), from a log Kow of 0.51(4) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low. Biodegradation data in water were not available(SRC, 2018).

According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), Ortho Phthalaldehyde, which has a vapor pressure of 5.2X10-3 mm Hg at 21 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase Ortho Phthalaldehyde is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 17 hours(SRC), calculated from its rate constant of 2.3X10-11 cu cm/molecule-sec at 25 °C(3). Ortho Phthalaldehyde has an absorption peak at 297 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of Ortho Phthalaldehyde with photochemically-produced hydroxyl radicals has been reported as 2.3X10-11 cu cm/molecule-sec at 25 °C(1). This corresponds to an atmospheric half-life of 17 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(2). Ortho Phthalaldehyde is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Ortho Phthalaldehyde has an absorption peak at 297 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for Ortho Phthalaldehyde(SRC), using a log Kow of 0.51(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of Ortho Phthalaldehyde can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that Ortho Phthalaldehyde is expected to have very high mobility in soil(SRC).

The Henry's Law constant for Ortho Phthalaldehyde is estimated as 1.8X10-8 atm-cu m/mole(SRC) derived from its vapor pressure, 5.2X10-3 mm Hg(1), and water solubility, 5.0X10+4 mg/L(1). This Henry's Law constant indicates that Ortho Phthalaldehyde is expected to be essentially nonvolatile from water and moist soil surfaces(2). Ortho Phthalaldehyde is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 3253 workers (2222 of these are female) were potentially exposed to Ortho Phthalaldehyde in the US(1). Occupational exposure to Ortho Phthalaldehyde may occur through dermal contact with this compound at workplaces where Ortho Phthalaldehyde is produced or used(SRC). Monitoring and use data indicate that the general population may be exposed to Ortho Phthalaldehyde via dermal contact with devices containing residual disinfectant(SRC). The median time-weighted average exposure to Ortho Phthalaldehyde in manual and automated endoscope disinfection workers was 0.66 and 0.33 ppb, respectively(2).

COMPOSITION
Ortho Phthalaldehyde (0,55%), benzotriazole, buffers, antioxidant and stabilising agents. Does not contain quaternary ammonium salts, chlorine, phenol.

MICROBIOLOGICAL PROPERTIES
Bactericide, fungicide, mycobactericide, virucide, sporicide.