Registration Dossier

Administrative data

Description of key information

Oral (OECD 401), rat: LD50 > 2000 mg/kg bw (limit test)

Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw (limit test)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 Feb - 06 Mar 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(1981)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks
- Weight at study initiation: males: 120 - 139 g; females: 122 - 138 g
- Housing: animals were housed in groups of five by sex in solid-floor polypropylene cages with sawdust bedding
- Diet: Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K., ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23
- Humidity (%): 39 - 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:
Preliminary study: 25, 200, 2000 and 5000 mg/kg bw
Main study: 2000 mg/kg bw
No. of animals per sex per dose:
Preliminary study: 1
Main study: 5
Control animals:
no
Details on study design:
Preliminary study:
- Duration of observation period following administration: 5 days
- Frequency of observations: Animals were observed 1 and 4 hours after dosing and then daily for 5 days.
- Necropsy of survivors performed: no

Main study:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for deaths and evidence of overt toxicity 1 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded on the day of treatment (day 0) and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Preliminary study:
The female rat dosed with 5000 mg/kg bw died on day 1. All other animals survived until the end of the study. From this mortality data the oral LD50 was considered to be approximately 5000 mg/kg bw and a dose level of 2000 mg/kg bw was selected for the main study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities were observed until the end of the study.
Clinical signs:
Common signs of toxicity noted on the first day were hunched posture, lethargy, piloerection, decreased respiratory rate and ataxia.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy of animals killed at the end of the study.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study in rats a LD50 value of > 2000 mg/kg bw was found.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
no analytical data, insufficient documentation, only summary available, only 2 animals tested
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(1981)
Deviations:
yes
Remarks:
no analytical data, insufficient documentation, only summary available, only 2 animals tested
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
mouse
Strain:
NMRI
Sex:
male
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

Doses:
250, 500, 1000, 2000 and 4000 mg/kg bw
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
The LD50 was determined graphically.
Sex:
male
Dose descriptor:
LD50
Effect level:
2 850 mg/kg bw
Based on:
test mat.
Remarks on result:
other: graphic determination
Mortality:
2/2 animals died in the high dose group (4000 mg/kg bw) 45 min to 4 h after test substance application. No mortalities were detected in the other dose groups.
Clinical signs:
Sedation, ataxia, dyspnea, ptosis, muscular hypotonia, tremor, side-and supine position were detected at and above 500 mg/kg bw.
Gross pathology:
Pale liver parenchyma and gritty kidney surface were detected.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study in rats a LD50 value of 2850 mg/kg bw was found.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Oral

The acute oral toxicity of the test substance was assessed in a study according to OECD Guideline 401 and in compliance with GLP (1990). Based on a preliminary study a total dose of 2000 mg/kg bw (limit test) was administered to 5 male and 5 female rats. Animals were observed for mortality and general clinical conditions 1 and 4 h after administration and once daily thereafter for 14 days. Body weights were recorded on the day of administration and on days 7 and 14. Macroscopic examination was performed in the end of the observation period at terminal sacrifice. None of the animals died. Common signs of toxicity noted during the day of dosing were hunched posture, lethargy, piloerection and decreased respiratory rate. An isolated incident of ataxia was also noted 1 h after dosing. The body weight gain was not affected by the administration of the test substance. No abnormalities were observed at necropsy. Based on the results of this study, the oral LD50 value was determined to be > 2000 mg/kg bw in rats.

In a supporting study, the acute oral toxicity of the test substance was assessed equivalent to OECD Guideline 401 in mice (1979). Doses of 250, 500, 1000, 2000 and 4000 mg/kg bw test substance were administered to 2 male mice each. Two animals died at 4000 mg/kg bw 45 min to 4 h after dosing after they were found in a comatose state. No mortalities occurred in the other dose groups. Clinical signs observed at and above 500 mg/kg bw were sedation, ataxia, dyspnea, ptosis, muscular hypotonia, tremor, side-and supine position. In necropsy pale liver parenchyma and gritty kidney surface were detected. Based on the results of this study, the graphically determined oral LD50 value was 2850 mg/kg bw in mice.

 

Dermal

The acute dermal toxicity of the test substance was assessed in a limit test performed in 5 male and 5 female Wistar rats according to OECD Guideline 402 and in compliance with GLP (1999). The test substance was applied at a single dose of 2000 mg/kg bw to the clipped skin of the animals and was then held in contact with a semi-occlusive dressing for 24 hours. Animals were observed for mortality, overt signs of toxicity and evidence of primary irritation for a 14-day period. Body weights were recorded prior to administration and on days 7 and 14 thereafter. Macroscopic examination was performed at the end of the observation period at terminal sacrifice. None of the animals died and no signs of systemic toxicity or signs of skin irritation were observed. The body weight gain was not affected by the administration of the test substance. No abnormalities were observed at necropsy. Based on the results of this study, the LD50 value for acute dermal toxicity was determined to be > 2000 mg/kg bw in rats.

Justification for classification or non-classification

The available data on acute oral and dermal toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.