Registration Dossier

Administrative data

Description of key information

Acute toxicity: oral, rat (male/female) (Guideline studies with various products containing different PAA concentrations):
- LD50: > 2000 mg/kg bw (male/female) (based on product (0.15% / 0.89% peracetic acid ))
- LD50: 185 to 3622/kg bw (male/female) (based on product (2.6 - 17% peracetic acid ))
- LD50: 50 - 500 mg/kg bw (male/female) (based on product (35% peracetic acid ))
Acute toxicity: inhalation, rat (male/female) (Guideline studies with various products containing different PAA concentrations):
- 4h-LC50: 204 mg/m³ (4080 mg/m³ based on product containing 5% peracetic acid )
- RD50: 5.4 ppm (17 mg/m³) pure peracetic acid (generated from a mixture of peracetic acid /HP/Acetic acid)
Acute toxicity: dermal (Guideline studies with various products containing different PAA concentrations):
- LD50: > 2000 mg/kg bw (rat, male/female) (based on product <1% peracetic acid )
- LD50: >1147 mg/kg bw (rabbit, male/female) (based on product ≥1% peracetic acid )

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
50 mg/kg bw
Quality of whole database:
Several reliable guideline studies with various dose concentrations of peracetic acid were avaialble.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
204 mg/m³
Quality of whole database:
Several reliable guideline studies with various dose concentrations of peracetic acid were avaialble.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 147 mg/kg bw
Quality of whole database:
Several reliable guideline studies with various dose concentrations of peracetic acid were avaialble.

Additional information

Acute toxicity: oral

A number of oral acute toxicity studies were carried out in rats using different products containing concentrations of PAA ranging from 0.15 to 35%. The studies were carried out in accordance with standard OECD/EU/US-EPA and international GLP guidelines.

Two studies were available, where PAA in concentrations <1% were tested. In the first one conducted by Freeman (1991a) rats were dosed with a solution containing 0.15 % peracetic acid at a dosage level of 5000 mg/kg of the product in a limit test. All animals remained healthy throughout the study and no internal lesions were observed in any animal at necropsy. The LD50 is >5000 mg/kg bw based on the product.

In the second study, rats were dosed with a peracetic acid solution with a concentration of 0.89% at dosage levels of 514, 1027 and 2054 mg/kg of the product, the LD50 value derived is > 2000 mg/kg bw (combined) (Den Besten, 1994).

Several studies were performed with products containing peracetic acid ranging from 2.6 - 6.11%, which showed LD50 values ranging from 185 to 3622 mg/kg bw based on the product (Rondot, 1984; Kynoch and Mullins, 1985; Kuhn, 1996a; Freeman, 1998; Haynes and Brightwell, 1998; Harrod, 1993). The most frequently observed clinical effects during the studies consisted of piloerection, respiratory difficulties, reduced activity and diarrhoea. The main observed effects at necropsy were abnormalities in the gastrointestinal tract including distended stomach and some changes in adjacent organs, e.g. liver. Similar effects were observed in studies with products with peracetic acid concentrations ranging from 10 - 11.7%, with LD50 values ranging from 652 to 2540 mg/kg bw based on the product (Kuhn, 1996b, Degussa, 1977).

Two studies with products containing PAA with concentrations of 15 and 17% were reported (Degussa, 1982; Morris, 1995), with LD50 values of 1026 and 1780 mg/kg bw, respectively, based on the product. The main clinical signs observed were oral and ocular discharges, respiratory distress and abdominal distention. The gross necropsy findings in the animals that died during the observation period in all these studies were those generally seen in response to the oral administration of a severely irritating and corrosive material.

In one study, a product containing 35% peracetic acid was tested. The LD50 value was between 50 and 500 mg/kg bw based on the product, as 10/10 and 1/10 died at these dose levels, respectively (Freeman, 1987).

Based on the component peracetic acid, the lowest LD50 was 9.0 mg/kg bw (Kuhn, 1996a), but on the other hand also LD50 values higher than 200 mg/kg bw have been reported. The variability of the LD50 determinations for similar products is probably due to methodological differences, particularly differences in the peracetic acid concentration and volume of the test material solutions applied by gavage. If the stock solution was diluted and a constant volume was administered, the toxicity was generally lower as compared to studies where undiluted test material was administered and/or volumes increasing with higher dose levels. So the LD50 was 185 mg/kg bw for a product containing 4.89% peracetic acid applied undiluted with volumes ranging from 0.04 to 4.5 ml/kg bw (Kuhn, 1996a), whereas the LD50 values ranged from 1270 to 1922 mg/kg bw in the other studies conducted with similar products (4.5 - 6.11% peracetic acid), but administered in higher (fixed) volumes containing lower concentrations of peracetic acid. In the study showing the highest LD50 (3622 mg/kg bw), coconut oil was used as vehicle, whereas water was used in all other studies. Similar differences were seen in the other study conducted by Kuhn (1996b) with a product containing 11.7% peracetic acid. Thus, it can be concluded that the toxicity is higher when tissue (including the GIT) is damaged due to the corrosive properties of peracetic acid at higher concentrations.

Interestingly, in the studies conducted by Kuhn (1996a, b) gas in the GIT was found on gross pathological examination. This finding supports the assumption made to explain the local irritation of trachea and lungs observed in the subchronic rat study conducted by Gaou (2003).

Overall it can be concluded that for peracetic acid concentrations <1% the oral LD50 is >2000 mg/kg bw, for peracetic acid concentrations of 2.6 - 17% the oral LD50 is from 185 to 3622/kg bw, and from concentration of ≥35 %, the oral LD50 is 50-500 mg/kg bw, respectively.

Acute toxicity: inhalation

The available acute inhalation studies with aerosols and vapour derived from different peracetic acid solutions suffered on the one hand from the general difficulty of generating and maintaining a stable atmosphere of peracetic acid, but also on the other hand of the difficulties to measure accurately the composition of the test atmosphere and particle size of the aerosol. The reported LC50 values should be therefore treated with circumspection. However, the common finding of those studies was local irritation of the respiratory tract, which seems more pronounced with aerosols than vapours.

In that sense, the following two studies testing peracetic acid at concentrations of 5% and 36%, respectively, were selected as key studies. While a number of available supporting studies show generally lower toxicity values (if derived), these are not discussed in detail.

In a GLP guideline study, Janssen and Van Doom (1994) tested a 5 % solution of peracetic acid in rats exposed nose-only to aerosols containing measured concentrations of 87, 163, 185 and 267 mg peracetic acid/m³. The 4 -hour LC50 was 204 mg peracetic acid/m³ (4080 mg/m³ based on product). Mortalities were observed only in the two highest dose groups. Clinical signs consisted of apathy, respiratory distress, reduced respiratory rates, decreased fear reaction, freezing and reduced locomotion activity. No macroscopic alterations were seen at necropsy carried out at the end of the observation period.

In addition, the study conducted by Gagnaire (2002) was selected as key study, in which the irritating power of "pure" peracetic acid and commercially available peracetic acid (a mixture of peracetic acid, acetic acid and hydrogen peroxide) was evaluated. Effects were further compared to that of acetic acid and hydrogen peroxide using a quantitative methodology initially developed to test the sensory irritation properties of airborne chemicals in mice. The method used was based on the observation that irritants stimulate the trigeminal nerve endings in the nasal mucosa of oronasally exposed mice which causes a characteristic reflex leading to a decreased respiratory rate. The decrease is directly related to the exposure concentration. The concentration causing a 50 % decrease in the respiratory rate, i.e. the RD50, was used to compare the irritant potencies of peracetic acid, acetic acid and hydrogen peroxide, respectively, and to establish acceptable exposure levels. RD50 values have been successfully shown to predict safe industrial exposures if sensory irritation is the most sensitive endpoint. Therefore, the RD50 can be used as a basis for the determination of threshold limit values (TLVs).

Following this, the results of this study demonstrated that the sensory irritation potency as derived by the RD50 after a 1 hour exposure of male mice towards vapours of hydrogen peroxide, acetic acid a mixture of peracetic acid and pure paracetic. The RD50s derived for acetic acid (100%), hydrogen peroxide (30%) and a peracetic acid mixture (containing 36% peracetic acid, 53% acetic acid, 11% hydrogen peroxide) as well as pure peracetic acid were 227 ppm (560 mg/m3), 113 ppm (157 mg/m3), 10.6 ppm (3.8 ppm or 12 mg/m3 with respect to peracetic acid only) and 5.4 ppm (17 mg/m3), respectively. Using the additivity rule, the theoretical RD50 was calculated to be 14.3 ppm for the peracetic acid mixture (containing 36% peracetic acid) or 5.1 ppm with respect to peracetic acid alone which is close to the experimental value of 3.8 ppm for peracetic acid in the mixture. Although a contribution of hydrogen peroxide and acetic acid in the mixture cannot be entirely excluded, this is considered to be unlikely because the concentrations of these two chemicals are relatively low in terms of their irritant potency and when compared to the RD50s determined for 100% acetic acid and 30% hydrogen peroxide, respectively.

Together the data of the available acute inhalation toxicity studies revealed the calculated LC50 of 204 mg /m³ for 100% PAA. Moreover, a RD50 of 5.4 ppm was estimated, which is used for the risk assessment.

Acute toxicity: dermal

Several dermal toxicity studies were carried out in rats and rabbits with aqueous solutions of peracetic acid at concentrations ranging from 0.15 to 17 %. The studies were carried out in accordance with standard OECD/EU/US-EPA and international GLP guidelines. The acute dermal LD50 of formulations containing 5 - 15% peracetic acid was greater than 400 mg/kg bw in the rat and between 200 and 2000 mg/kg bw in the rabbit if based on the product. During many studies only one dose was tested, which did not result in any mortality. However, during the studies of Kuhn (1996c,d) mortality was found and they reported LD50 values of 1147 mg/kg bw based on the product (4.89% PAA) and 1957 mg/kg bw based on the product (11.7% PAA) for rabbits, corresponding to 56.1 and 228.8 mg/kg bw peracetic acid, respectively. It is important to stress out that the observed dermal toxicity depends on the degree of skin damage caused by the different peracetic acid solutions, since the corrosive properties of PAA may compromise the integrity of the skin. Based on this, the overall data suggest a dermal LD50 of >2000 mg/kg bw for peracetic acid <1% and a dermal LD50 of >1147 for peracetic acid at concentrations ≥1%.


Justification for selection of acute toxicity – dermal endpoint
The available data on acute oral, inhalative and dermal toxicity of peracetic acid meet the criteria for classification according to Regulation (EC) 1272/2008 resulting in classifications with respective concentrations limits as follows:

Justification for classification or non-classification

The available data on acute oral, inhalative and dermal toxicity of peracetic acid meet the criteria for classification according to Regulation (EC) 1272/2008 resulting in classifications with respective concentrations limits as follows:

Oral

C < 1%

No classification

1 ≤ C <35%

Acute Tox. 4

C ≥35%

Acute Tox. 3

Inhalative

C ≥ 1%

STOT SE3 / H335

C < 5%

No classification

5% ≥ C > 20%

Acute Tox. 4

C ≥ 20%

Acute Tox. 3

Dermal

C < 1%

No classification

C ≥ 1%

Acute Tox. 4