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Description of key information

Acute oral toxicity. Key study: Test method EU method B.1 bis. GLP study. The LD50 in rats was determind to be > 2000 mg/kg bw. Diverse clinical signs were recorded but were transient and all animals appeared normal by day 6 post-dosing.
Acute dermal toxicity. Key study: Test method EU method B.3. GLP test. The LD50 in rats was determined to be > 2000 mg/kg bw. No adverse effects were observed.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test method equivalent to EU method B.1 bis. GLP study.
Qualifier:
equivalent or similar to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Fasting period before study: Yes.
Route of administration:
oral: gavage
Vehicle:
not specified
Doses:
2000 mg/kg body weight.
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Observations for clinical signs were made twice daily. Body weights were recorded on day 1 (prior to dosing), 2, 3, 4, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopical observations, clinical signs, body weights.
Statistics:
The LD50 value, and where possible, the value of males and females separately, was calculated from the observed mortality data, using established procedures.
Preliminary study:
The main test is a limit test, performed at a concentration of 2000 mg/kg body weight.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred.
Clinical signs:
Clinical signs of toxicity included abnormal gait, lethargy, decreased respiratory rate, increased salivation, pallor of the extremities, blue color to the skin and extremities, cold body surfaces and prostration seen in all or the majority of the rats. These signs were transient with all animals appearing normal by day 6 post dosing.
Body weight:
Minor transient fluctuations in bodyweight.
Gross pathology:
No remarkable observations.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results, the oral DL50 for the test substance in rat is greater than 2000 mg/kg body weight.
Executive summary:

An acute oral toxicity study was performed with a method equivalent to EU method B.1 bis under GLP conditions. A group of ten rats (5 males and 5 females) was exposed to the test substance in single oral dose by gavage at a dose level of 2000 mg/ kg body weight. Animals were observed for 14 days and then sacrificed and examined macroscopically. No deaths occurred, clinical signs of toxicity observed included abnormal gait, lethargy, decreased respiratory rate, increased salivation, pallor of the extremities, blue color to the skin and extremities, cold body surfaces and prostration seen in all or the majority of the rats. These signs were transient with all animals appearing normal by day 6 post dosing. There were also minor fluctuations in body weights. Based on the results the oral LD50 for the test substance in rat is greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The study is GLP compliant and has high quality (Klimish 1).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
9 May to 23 May, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test method according to EU method B.3. GLP study.
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac Ltd., Bicester, Oxon, England.
- Age at study initiation: 7-10 weeks.
- Weight at study initiation: 214-238g.
- Housing: individually housed in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): Ad libitum. SDS LAD 1, a standard laboratory rodent diet.
- Water (e.g. ad libitum): Ad libitum.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature : 22+/- 3 ºC.
- Humidity : 30-70%.
- Air changes : 10 to 15 air changes per hour.
- Photoperiod: 12hrs dark / 12hrs artifical light.

IN-LIFE DATES: From 9 May 1995 to 23 May 1995.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorso-lumbar region (clipped one day prior treatment).
- Treated area: The test substance was applied by spreading it evenly over the prepared skin (50mmx50mm).
- Type of wrap if used: The treated area was covered with gauze which was held in place with a non-irritative dressing encircled firmly around the truck.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water (30º to 40ºC) and blotted dry with absorbent paper.
- Time after start of exposure: 24h.

TEST MATERIAL
- Amount(s) applied: 2.0 g/kg body weight.

Duration of exposure:
24 h.
Doses:
2.0 g/kg bw.
No. of animals per sex per dose:
5/sex/dose.
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Mortality was checked at least twice daily. Animals were observed for clinical signs soon after dosing and at frequent intervals for the remainder of Day 1 (a period of five hours). On subsequent days animals were observed once in the morning arid again at the end of the experimental day. Local dermal irritation at the treatment site was assessed daily using Draize numerical scoring. Individual body weights were recorded on day 1 (prior to dosing), 8 and 15. All animals were killed on day 15 and were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of all examined tissues was recorded.
Statistics:
The LD50 value, and where possible, the value of males and females separately, was calculated from the observed mortality data, using established procedures.
Sex:
male/female
Dose descriptor:
LDLo
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths following a single dermal application of OS-2200 to a group of ten rats at a dosage of 2.0 g/kg bw.
Clinical signs:
There were no signs of systemic reaction to treatment.
Body weight:
In comparison with historical data from the Department of Industrial Toxicology of HRC, slightly low body weight gains were recorded for two males and two females on Day 8. All other rats achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No macroscopic abnormalities were observed for animals killed on day 15.
Other findings:
Sites of application showed no irritation or other dermal changes.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute lethal dermal dose to rats was found to be greater than 2.0 g/kg bw.
Executive summary:

An acute dermal toxicity study was performed according to EU method B.3 under GLP conditions. A group of ten rats (5 males and 5 females) was dermally exposed to 2.0 g/ kg bw of OS-2200 for 24 hours. Animals were observed for 14 days and there were no deaths, signs of systemic reaction or dermal changes in sites of application. Animals were killed on day 15 and subjected to a macroscopic examination: there were no macroscopic abnormalities. The acute lethal dermal dose to rats was found to be greater than 2.0 g/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The study is GLP compliant and has (Klimish 1).

Additional information

Acute oral toxicity: Key study: An acute oral toxicity study was performed with a method equivalent to EU method B.1 bis (GLP study). A group of ten rats (5 males and 5 females) was exposed to the test substance in single oral dose by gavage at a dose level of 2000 mg/ kg body weight. No deaths occurred. Clinical signs including abnormal gait, lethargy, decreased respiratory rate, increased salivation, pallor of the extremities, blue color to the skin and extremities, cold body surfaces and prostration seen in all or the majority of the rats were transient with all animals appearing normal by day 6 post dosing. Based on the results, the oral LD50 in rat was greater than 2000 mg/kg bw.

Acute dermal toxicity: Key study: An acute dermal toxicity study was performed according to EU method B.3 (GLP study). A group of ten rats (5 males and 5 females) was dermally exposed to 2000 mg/ kg bw of test item for 24 hours. Animals were observed for 14 days and there were no deaths, signs of systemic reaction or dermal changes in sites of application. Animals were killed on day 15 and no no macroscopic abnormalities were observed. The acute lethal dermal dose to rats was found to be greater than 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Based on the available data (LC50 > 2000 mg/kg bw), the substance is not classified for Acute Toxicity in accordance with CLP Regulation (EC) No. 1272/2008.