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Administrative data

Description of key information

Acute toxicity: lowest oral: LD50 =  1670 mg/kg bw (pre-OECD and pre-GLP, WoE, rel. 4) in rats;
Acute toxicity: dermal: LD50 > 5000 mg/kg bw (similar to OECD 402, K, rel. 2) in rabbits.

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:
weight of evidence
Study period:
1964
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
Pre-guideline and pre-GLP study. Only basic data given but considered sufficient for a weight of evidence (purity not reported, test system details not reported; body weight and gross pathology not reported).
Principles of method if other than guideline:
Rats were given a single oral dose of test item and then observed for 14 days.
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: rats: 180-350 g
- Fasting period before study: 18 hours
- Diet, ad libitum
- Water, ad libitum
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Not reported
Doses:
No data
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: The rats were observed until the survivors had returned to normal in appearance and weight
Statistics:
LD50s were computed by the method of Litchfield and Wilcoxon (1949).
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 670 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 265 - <= 2 200
Mortality:
Animals died within 4 hours to 2 days after treatment.
Clinical signs:
Rough fur, depression
Body weight:
No data
Gross pathology:
No data

None

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the test conditions, test material is classified Category 4 (H302: Harmful if swallowed) according to the Regulation (EC) No. 1272/2008 and of the GHS as the LD50 value is comprised between 300 and 2000 mg/kg bw.
Executive summary:

In an acute oral toxicity study, rats (5/sex/dose) were administered the test substance by gavage with a stomach tube. Animals were then observed for mortality and clinical signs for 14 days.

Deaths occurred between 4 hours and 2 days and clinical signs were reported to be rough fur and depression.

Combined oral LD50 = 1670 mg/kg bw (95% CL 1265 -2200 mg/kg bw).

 

Under the test conditions, test material is classified Category 4 (H302: Harmful if swallowed) according to the Regulation (EC) No. 1272/2008 and of the GHS as the LD50 value is comprised between 300 and 2000 mg/kg bw.

This study is considered as sufficiently reliable in a weight of evidence approach for the purpose of acute oral toxicity endpoint.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1972
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
Pre-guideline and pre-GLP study. Only basic data given but considered sufficient for a weight of evidence (purity not reported, test system details not reported; body weight and gross pathology not reported)
Principles of method if other than guideline:
Standard acute method
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200-250 g
- Fasting period before study: Animals were fasted for a minimum of 16 hours prior to administration of test item.
- Diet, ad libitum
- Water, ad libitum
Route of administration:
oral: unspecified
Vehicle:
water
Details on oral exposure:
DOSAGE PREPARATION: Test item was administered as a 30% slurry in water.
Doses:
1600, 2020, 2560 and 3200 mg/kg bw
No. of animals per sex per dose:
10 males/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Observations for mortality were made at 1 and 6 hours after dosing and daily thereafter for 14 days.
- Necropsy of survivors performed: Yes; gross necropsies were performed on all survivors
Statistics:
None
Preliminary study:
Not applicable
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2 600 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 300 - <= 2 900
Mortality:
Mortality was observed in 0/10, 1/10, 6/10 and 10/10 at 1600, 2020, 2560 and 3200 mg/kg bw, respectively. Deaths occurred overnight to three days following administration of the test item.
Clinical signs:
Animals experienced ataxia, loss of righting reflex and slow respiration.
Body weight:
No data
Gross pathology:
No data
Other findings:
None

None

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Under the test conditions, oral LD50 of test item is 2600 mg/kg bw (95% CL: 2300 to 2900 mg/kg bw) in male rats, therefore it is not classified according to the Regulation (EC) No. 1272/2008 but is classified in Category 5 (2000 < LD50 <5000 mg/kg bw) according to the GHS.
Executive summary:

In an acute oral toxicity study, ten male rats were given a single oral dose of test item at 1600, 2020, 2560 and 3200 mg/kg bw. Animals were observed for mortality and clinical signs for 14 days.

Animals experienced ataxia, loss of righting reflex and slow respiration. Deaths occurred overnight to three days following administration of the test item. Mortality was observed in 0/10, 1/10, 6/10 and 10/10 at 1600, 2020, 2560 and 3200 mg/kg bw, respectively. In this study, the oral LD50 of test item was 2600 mg/kg bw (95% CL: 2300 to 2900 mg/kg bw) in rats.

Under the test conditions, oral LD50 of test item is 2600 mg/kg bw (95% CL: 2300 to 2900 mg/kg bw) in male rats, therefore it is not classified according to the Regulation (EC) No. 1272/2008 but is classified in Category 5 (2000 < LD50 <5000 mg/kg bw) according to the GHS.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 670 mg/kg bw
Quality of whole database:
Two studies were available on the substance. The two studies were not sufficiently reliable as such (Klimisch = 4) but were considered sufficiently reliable in a weight of evidence for the purpose of hazard assessment. The study having the lowest LD50 was taken as the key value for this endpoint.

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:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study conducted pre-GLP and pre-GLP but performed similarly to OECD Guideline 402 with deviations: purity of test item not reported; source and sex of animals and environmental conditions not reported; acclimation period not reported; observation period was 7 days instead of 14 days.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
purity of test item not reported; source and sex of animals and environmental conditions not reported; acclimation period not reported; observation period was 7 days instead of 14 days
Principles of method if other than guideline:
standard acute method
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.9-2.2 kg
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Clipped abraded abdominal skin
- Type of wrap if used: Animals were wrapped with binders of rubber dam, gauze and adhesive tape.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg bw
Duration of exposure:
24 h
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10 animals
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: Yes; gross necropsy was performed on all animals at the termination of the study.
Statistics:
None
Preliminary study:
Not applicable
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No clinical signs were observed.
Body weight:
Body weight evolution of the animals remained normal throughout the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Slight to moderate erythema and edema were noticed throughout the observation period.

None

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the dermal LD50 of test item is higher than 5000 mg/kg bw in rabbits therefore it is not classified according to the Regulation (EC) No. 1272/2008 and to the GHS.
Executive summary:

In an acute dermal toxicity study performed pre-GLP and pre-OECD but conducted similarly to OECD Guideline 402, a group of New Zealand white rabbits (10 animals/dose) were given a single dermal application of Compound No. 72-22 at 5000 mg/kg bw. The test item was applied to the abraded abdominal skin. The test site was then covered by a semi-occlusive dressing for 24 h. Animals were then observed for mortality, clinical signs and bodyweights for 7 days and were all sacrificed for macroscopic examination.

No mortality or clinical signs was observed. Slight to moderate erythema and edema were noticed throughout the observation period. Body weight evolution of the animals remained normal throughout the study. No abnormalities were noted at necropsy. The dermal LD50 of test item was considered to be higher than 5000 mg/kg bw in rabbits.

Under the test conditions, the dermal LD50 of test item is higher than 5000 mg/kg bw in rabbits therefore it is not classified according to the Regulation (EC) No. 1272/2008 and to the GHS.

This study is acceptable and satisfies the requirements for acute dermal toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw
Quality of whole database:
The key study performed in rats was pre-GLP and pre-OECD, but was similar to OECD Test Guideline No 402. This study was considered sufficiently robust to cover this endpoint.

Additional information

Acute toxicity: oral

Two studies were available on the substance. The two studies were not sufficiently reliable as such (Klimisch = 4) but were considered sufficiently reliable in a weight of evidence for the purpose of hazard assessment.

In the first study (Jenner, 1964, rel. 4), the combined rat LD50 was calculated to be 1670 mg/kg [1265 -2200 mg/kg bw]. Deaths occurred between four hours and two days and clinical signs were reported to be rough fur and depression. The test item was a liquid and was administered undiluted, but no attempt was made to secure chemically pure compounds.

In the second study (Toxicological ressources, 1972, rel. 4), the male rat LD50 was calculated to be 2600 mg/kg bw. Animals experienced ataxia, loss of righting reflex and slow respiration. Deaths occurred overnight to three days following administration of the test item. Mortality was observed in 0/10, 1/10, 6/10 and 10/10 at 1600, 2020, 2560 and 3200 mg/kg bw, respectively. The test item was a powder and was administered as a 30% slurry in water.

As a worst-case, the lowest LD50 was taken as the key value for this endpoint.

Acute toxicity: dermal

A key study was identified (Toxicological ressources, 1972, rel.2). In this acute dermal toxicity study performed pre-GLP and pre-OECD, but conducted similarly to OECD Test Guideline No 402, a group of New Zealand white rabbits (10 animals/dose) were given a single dermal application of the test item at 5000 mg/kg bw on the abraded abdominal skin. The test site was then covered by a semi-occlusive dressing for 24 h. Animals were then observed for mortality, clinical signs and bodyweights for 7 days and were all sacrificed for macroscopic examination.

No mortality or clinical signs was observed. Slight to moderate erythema and edema were noticed throughout the observation period. Body weight evolution of the animals remained normal throughout the study. No abnormalities were noted at necropsy.

The dermal LD50 of test item was considered to be higher than 5000 mg/kg bw in rabbits.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self-classification:

Acute toxicity via Oral route:

Based on the available data, as a worst-case, the substance is classified in Category 4 (H302: Harmful if swallowed) according to the Regulation (EC) No. 1272/2008 and of the GHS as the LD50 is 1670 mg/kg bw (300 < LD50 < 2000 mg/kg bw).

Acute toxicity via Dermal route:

Based on the available data, the substance is not classified according to the Regulation (EC) No. 1272/2008 and of the GHS as the LD50 is above 5000 mg/kg bw.

Acute toxicity (Inhalation):

No data was available

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the Annex VI of the Regulation (EC) No 1272/2008 as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (dermal) for a Category 1 classification (C≤ 1000 mg/kg bw) and at the guidance value (dermal) for a Category 2 classification (2000 mg/kg bw≥C > 1000 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute dermal toxicity study.

Specific target organ toxicity: single exposure (Inhalation):

No data was available