Registration Dossier

Administrative data

Description of key information

Acute oral toxicity:  No deaths seen at 5000 mg/kg bodyweight in rats.
Acute inhaled toxicity: No deaths seen in rats exposed to 0.52 mg/L air for 4 hours.
Acute dermal toxicity: No deaths seen in rats exposed at 2000 mg/kg for 24 hours.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
discriminating conc.
Value:
520 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity

An acute oral toxicity test was performed to determine the acute toxicity by oral exposure of ADCA (tested under the name of Unifoam AZ SO-NL)(HLS 1988, OCI64/88720D). The study was conducted in accordance with relevant EC and OECD test guidelines, and in compliance with GLP.

A group of ten rats (five male and five female) were dosed with 5000 mg test substance/kg bodyweight by oral gavage, then observation for mortality and clinical signs performed over a period of 14 days. At the end of the observation period, all animals were sacrificed and postmortem examinations performed.

No deaths occured in the test rats. Piloerection and hunched posture were seen in all rats within five minutes of dosing, and piloerection persisted for the remainder of the day of dosing; all animals had recovered by day 2 and no further unusual clinical signs were seen. Slightly low bodyweight gains were recorded for two male and one female rat, however all other rats made the anticipated weight gains. Terminal autopsy findings were normal.

The acute lethal oral dose to rats of Unifoam AZ SO-NL was found to be greater than 5.0 g/kg bodyweight.

 

Acute inhalation toxicity

One study report on rat is available and results are supported by a publication of a study realised on guinea pigs.

 

The study report is an acute toxicity study was conducted to assess the toxicity of ADCA (tested under the name of UNIFOAM AZ SO-NL) after acute inhalation exposure (HLS 1988, 881087 -OCI43). The study was conducted in compliance with GLP.

Five male and five female rats were exposed by whole body exposure to an atmosphere containing the test material as an airborne dust for an exposure period of four hours. A concurrent control group was exposed in a similar fashion to untreated air. Following the exposure process, animals were observed for 14 days, sacrificed, then a necroscopic examination performed.

There were no deaths during the study. Test substance residues were seen on the fur of most of the exposed rats for 3 days following exposure; all rats were normal by day 7 of the observation period. Body weight gains and the ratio of lung weight to bodyweight were unaffected by exposure to ADCA, and no macroscopic or microscopic abnormalities were seen during pathology. Analysis of the test atmosphere determined that the mean atmospheric concentration of the test substance during the exposure period was 0.52 mg/L.

The 4-hour LC50 was estimated to be in excess of 0.52 mg/L of air. This was the highest airborne concentration that could be produced using the procedures employed.

 

In an article published by Shopp , 1987, the effects of inhalingon lung structure and function of guinea pigs were examined during and after an acute exposure in guineapigs. Groups of 20 guineapigs were exposed to each of 3 concentrations of ADCA (19, 58, and 97 mg/m3) , plus air as a control, for 1 hr. Pulmonary function was measured before exposure (baseline), during exposure, immediately after exposure and 24 hr after exposure. Dynamic compliance (Cdyn), total pulmonary resistance (RL), tidal volume (VT), respiratory frequency and minute volume were measured. In addition, gross necropsies and histological examinations of respiratory tract tissues were done either immediately following the exposure or 24 hr after exposure. There were no effects of exposure on gross necropsy, histology, Cdyn, or RL. Some significant, concentration-related decreases in VT, respiratory frequency and minute volume were seen. The magnitudes of these changes were small: the largest change was seen in minute volume, amounting to a 24% decrease in the high concentration group. Inhalation exposure of guinea pigs to ADCA at concentrations of up to 97 mg/m3 resulted in minor changes in pulmonary function without and changes in lung histology.

 

 

Acute dermal toxicity

Two studies have been realised in rats and in rabbits for the evaluation of the acute dermal toxicity of ADCA, both according to protocols similar to international recognised guidelines.

 

In the first study, the toxicity of ADCA (tested under the name of Unifoam AZ SO-NL) was assessed after acute dermal exposure (HLS 1988, 88726D-OCI 65 -AC). The study was conducted in accordance with EC and OECD test guidelines, and in compliance with GLP.

Ten rats (five males and five females) were exposed to the test substance by dermal exposure at 2.0 g/kg bodyweight for a period of 24 hours. At the end of the exposure period, the test substance was washed off, and the test animals were observed for mortality, clinical signs and signs of dermal irritation for a period of 14 days after exposure. At the end of the observation period, all test animals were sacrificed and post mortem examinations were performed.

No deaths occurred in the test animals during the exposure or observation periods. No clinical signs or dermal responses were observed, and terminal autopsy results were normal. Slightly low bodyweight gains were seen in two male and two female rats at the end of the observation period.

The acute lethal dermal dose to rats of Unifoam AZ SO-NL was found to be greater than 2.0 g/kg bodyweight.

 

In the second test, five healthy male and five healthy female New Zealand Albino rabbits were dosed dermally with ADCA (tested under the name of Celogen AZ 120) at 2.0 g/kg of body weight (MB Research Labs 1986, 86 -8393B). The test article was kept in contact with the skin for 24 hours. Dermal responses were recorded days 1, 7 and 14. Animals were observed for toxicity, mortality and pharmacological effects at 1, 2 and 4 hours post dose and twice daily for 14 days. Body weight recorded pretest, weekly and at termination. All animals were examined for gross pathology. Abnormal tissues were preserved in 10% buffered formalin for possible future microscopic examination.

All animals survived the 2.0 g/kg dermal application.

Physical signs of few feces and diarrhea were noted during the study. An ocular discharge was also noted in one animal for one day.

Body weight changes were normal in 9/10 animals. One male lost weight during the observation period.

Dermal reactions, slight on day 1, were absent to slight on day 7 and absent on day 14.

Necropsy results were normal in 8/10 animals. Intestinal abnormalities were noted in the remaining two animals.

The rabbit dermal LD 50 is greater than 2.0 g/kg of body weight. 

Justification for classification or non-classification

The acute toxicity results for ADCA (tested under the name Unifoam AZ SO-NL or Celogen AZ 120) were reviewed with reference to EC directive 67/548/EEC, and the EU interpretation of CLP, EU Regulation 1272/2008. On the basis that the available tests confirmed the oral LD50 value to be greater than 5000 mg/kg bodyweight, and the dermal LD50 value to be greater than 2000 mg/kg bodyweight, ADCA does not require classification as toxic by oral or dermal exposure.

No deaths were seen in animals exposed to ADCA by the inhaled route, however the concentration assessed was too low to confirm that classification of the test substance is not required. The test was conducted at the maximum achievable airbourne concentration, 0.52 mg/L, however classification applies at levels up to 5 mg/L, and so this result is inconclusive.