Registration Dossier

Administrative data

Description of key information

Three studies differing in the route of exposure were performed to investigate the acute toxicity of the test item in male rats:

Key_acute oral_1973_Sandoz_13/73

Sup_acute dermal_1973_Sandoz_73/73

Sup_intraperitoneal_1973_Sandoz_73/73

Although each of these tests is poorly documented in terms of e.g. test design and details on test animals, the set in its entirety fulfills all requirements of a fully valid study thus allowing the conclusion that the test item exerts no acute toxicity.

 

Justification for selection of acute toxicity endpoint
No single study was selected because in view of different shortcomings in all available studies preference is given to the entirety of all available studies in order to get a fully valid data set.

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
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
poor documentation
Qualifier:
no guideline followed
Version / remarks:
Study pre-dates creation of guidelines, but a method similar to OECD 401 is likely
Principles of method if other than guideline:
Treatment of rats via gavage with subsequent observation
GLP compliance:
no
Remarks:
pre-guideline study
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
dionized
Details on oral exposure:
- Concentration in vehicle: ca. 33 %
- Amount of vehicle (if gavage): 15 mL per kg bw
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
not specified
Control animals:
not specified
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality observed
Clinical signs:
none reported
Interpretation of results:
GHS criteria not met
Remarks:
Regulation (EC) no 1272/2008
Conclusions:
The acute oral median lethal dose (LD50) of the test item in male rats was determined to be greater than 5000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).
The test item did not meet the criteria for classification according to Regulation (EC) No. 1272/2008.
Executive summary:

In a pre-guideline study the acute oral toxicity was investigated in white male rats.

The acute oral median lethal dose (LD50) of the test item in male rats was determined to be greater than 5000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).

The test item did not meet the criteria for classification according to Regulation (EC) No. 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The study is poorly documentd but the findings and conclusions are sufficiently supported by consideration of oral, dermal and intrapertoneal studies, which all show no adverse efffects even after intraperitoneal injection.

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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
poor documentation
Qualifier:
no guideline followed
Version / remarks:
study pre-dates creation of guidelines but a method similar to OECD TG 402 is likely
Principles of method if other than guideline:
4 hours dermal treatment with subsequent observation
GLP compliance:
no
Remarks:
pre-guideline study
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
- Weight at study initiation: 260 - 280 g (mean 270 g)
Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: 25 cm2
- Type of wrap if used: gauze patch, covered with plastic

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg bw

- For solids, paste formed: moistened with propylene glycol
Duration of exposure:
4 hours
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
4 males
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: after 4 hours, 2, 6, 9, 13 and 14 days
- Frequency of weighing: after 2, 6, 9, 13, 14 days
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality observed
Clinical signs:
at the first two readings after 4 hours and 2 days the treated skin was discoloured by the test material. In addition, reddened skin was noted in 2 animals.
Body weight:
All animals showed expected gains in body weight over the observation period.
Interpretation of results:
GHS criteria not met
Remarks:
Regulation (EC) No. 1272/2008
Conclusions:
The acute oral median lethal dose (LD50) of the test item in male rats was determined to be greater than 5000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).
The test item did not meet the criteria for classification according to Regulation (EC) No. 1272/2008.
Executive summary:

In a pre-guideline study the acute dermal toxicity was investigated in 4 male rats.

In a limit test the acute oral median lethal dose (LD50) of the test item in male rats was determined to be greater than 5000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).

The test item did not meet the criteria for classification according to Regulation (EC) No. 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Additional information

In a further study the test material was administered by the intraperitoneal route. The determined LD50 was greater than 5000 mg/kg bw. No adverse effects at all were reported after i.p. injection.

Justification for classification or non-classification

For all routes of exposure - oral, dermal and intraperitoneal - the determined median lethal dose is greater than 5000 mg/kg bw.

Thus, the test item has not to be classified for acute toxicity according to Regulation (EC) no 1272/2008.