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Description of key information

In an acute oral toxicity study (similar to OECD guideline 401) performed in mice, the LD50 was between 1960 and 4900 mg/kg bw.
In an acute dermal toxicity study (similar to OECD guideline 402) performed in rabbits, the LD50 was higher than 2000 mg/kg bw.

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:
28 February – 20 May 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study similar to OECD Guideline No 401 with deviations: no data test substance purity, no certificate of analysis ; no. of animals at two dose levels < 5; no details on environmental conditions; observation period of 7 days instead of 14 days.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(no data about test substance purity and no certificate of analysis; no. of animals at two dose levels < 5; no details on environmental conditions; observation period: 7 days)
Principles of method if other than guideline:
not applicable
GLP compliance:
no
Remarks:
pre-dating GLP regulation
Test type:
standard acute method
Limit test:
no
Species:
mouse
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
Age at study initiation: 4-5 weeks
Housing: animals were housed in individual cages.
Fasting period before study: 4 h
Diet: commercial pelleted diet, ad libitum
Water: ad libitum
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME ADMINISTERED: 10 mL/kg bw
Doses:
2, 5 and 10 mL/kg bw (equivalent to 1960, 4900 and 9800 mg/kg bw)
No. of animals per sex per dose:
5 mL/kg bw: 3/sex/dose
2 and 10 mL/kg bw: 1/sex/dose
Control animals:
no
Details on study design:
Duration of observation period following administration: 7 days
Any animal dying during the test was autopsied.
Survivors were weighed before killing for post-mortem examination at the end of the one week observation period.
Statistics:
none
Preliminary study:
not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 - 5 mL/kg bw
Based on:
test mat.
Remarks on result:
other: equivalent to 1960-4900 mg/kg bw; specific gravity: 0.98
Mortality:
Mortalities at 2, 5 and 10 mL/kg were 0, 100 and 100 %, respectively.
Clinical signs:
other: Mice dosed at all three levels were hypothermic and showing signs of stress within 30 minutes after treatment. Females dosed 5 and 10 mL/kg bw were also somnolent and exhibiting laboured breathing. Within 1 h after treatment all the male mice were somno
Gross pathology:
Autopsy of the animals that died revealed irritation of the small intestine and peritoneum; and the mesenteric lymph nodes of these animals also appeared enlarged and inflammed.

Livers and kidneys of these animals were pale, and they had distended bladders.
Other findings:
none

none

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 of nopyl acetate could be considered as higher than 2000 mg/kg bw in mice therefore it is not classified for acute oral toxicity according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.
Executive summary:

In an acute oral toxicity study (similar to OECD Guideline No 401), 3 groups of 1, 3 and 1 mice/sex were given a single oral dose of nopyl acetate at 2, 5 and 10 mL/kg bw, respectively. Animals were then observed for mortality, clinical signs and bodyweights for 7 days and were all macroscopically necropsied after sacrifice.

Mortalities at 2, 5 and 10 mL/kg bw were 0, 100 and 100 %, respectively. Surviving animals gained weight during the 7 day observation period and presented a normal appearance at autopsy. Mice dosed at all three levels were hypothermic and showing signs of stress within 30 minutes after treatment. Female dosed 5 and 10 mL/kg bw were also somnolent and exhibiting laboured breathing. Within 1 hr after treatment all the male mice were somnolent and the females dosed at 5 and 10 mL/kg bw were comatose. Within 2 hr after treatment all mice dosed at 5 and 10 mL/kg bw were cyanosed and after 18 h all these animals were dead. Mice dosed at 2 mL/kg bw were still showing signs of stress 18 h after treatment, but recovered within 42 h. Autopsy of the animals that died revealed irritation of the small intestine and peritoneum; and the mesenteric lymph nodes of these animals also appeared enlarged and inflammed. Livers and kidneys of these animals were pale, and they had distended bladders. In this study, the combined oral LD50 of nopyl acetate was considered to be 2-5 mL/kg bw (equivalent to 1960-4900 mg/kg bw) in mice.

The oral LD50 of nopyl acetate could be considered as higher than 2000 mg/kg bw in mice therefore it is not classified for acute oral toxicity according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Study performed similarly to OECD Guideline No 401 with deviations but considered as appropriate and reliable to complete 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 similar to OECD Guideline No 402 with deviations: no data about purity and no test substance certificate of analysis ; no data on age, gender and source of animals; no data on housing and environmental conditions; observation period: 7 days instead of 14; performed on abraded skin
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
no data about purity and no certificate of analysis of test substance; no data on age, gender and source of animals; no data on housing and environmental conditions; observation period: 7 days; performed on abraded skin
Principles of method if other than guideline:
not applicable
GLP compliance:
no
Remarks:
pre-dating GLP regulation
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
Weight at study initiation: 1.9-2.4 kg
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
Area of exposure: clipped abraded abdominal skin
Type of wrap if used: wrapped with binders of rubber dam, gauze and adhesive tape
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
10 rabbits
Control animals:
not specified
Details on study design:
Mortality and toxic effects were observed for a period of 7 days.

Necropsy of survivors performed: Yes
Other examinations performed: dermal reactions: erythema, edema and atonia
Statistics:
no data
Preliminary study:
Not applicable
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality
Clinical signs:
other: No evidence of toxicity; all animals appeared normal at the end of the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Dermal reactions:
- slight erythema in 8, 4 and 1 animal on Days 1, 2 and 3, respectively; moderate erythema in 1 animal on Day 1
- slight edema in 8 and 4 animals on Days 1 and 2, respectively; moderate edema in 1 animal on Day 1
- complete recovery within 4 days
- no signs of atonia were observed during the study

none

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 of nopyl acetate is greater than 2000 mg/kg bw in rabbits therefore it is not classified for acute dermal toxicity according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.
Executive summary:

In an acute dermal toxicity study (limit test), a group of 10 New Zealand White rabbits were administered a single dermal dose of nopyl acetate at 2000 mg/kg bw on clipped abraded abdominal skin using an occlusive patch for 24 h. Animals were then observed for mortality, clinical signs, bodyweights and dermal reactions for 7 days and were all macroscopically necropsied after sacrifice.

 

No deaths occurred throughout the study. Normal body weight gain was observed in all animals. At necropsy, macroscopic examination of main organs showed no abnormalities. Adverse dermal reactions noted were slight to moderate erythema and edema, which completely recovered to normal within four days. The acute dermal LD50 was therefore greater than 2000 mg/kg bw under test conditions.

 

The acute dermal LD50 of nopyl acetate is greater than 2000 mg/kg bw in rabbits. Therefore it is not classified for acute dermal toxicity according to Directive 67/548/EEC and according to CLP Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Study performed similarly to OECD Guideline No 402 with deviations but considered as appropriate and reliable to complete this endpoint.

Additional information

In an acute oral toxicity study (similar to OECD Guideline No 401), 3 groups of 1, 3 and 1 mice/sex were given a single oral dose of nopyl acetate at 2, 5 and 10 mL/kg bw, respectively. Animals were then observed for mortality, clinical signs and bodyweights for 7 days and were all macroscopically necropsied after sacrifice. Mortalities at 2, 5 and 10 mL/kg bw were 0, 100 and 100 %, respectively. Signs of toxicity described included: hypothermia, stress, somnolence. All mice dosed at 5 and 10 mL/kg bw were cyanosed and died 18 h after the treatment.

The acute oral LD50 of nopyl acetate was considered to be between 2 and 5 mL/kg bw (equivalent to 1960-4900 mg/kg bw) in mice.

In an acute dermal toxicity study (limit test), a group of 10 New Zealand White rabbits were administered a single dermal dose of nopyl acetate at 2000 mg/kg bw on clipped abraded abdominal skin using an occlusive patch for 24 h. Animals were then observed for mortality, clinical signs, bodyweights and dermal reactions for 7 days and were all macroscopically necropsied after sacrifice. No deaths occurred throughout the study. Normal body weight gain was observed in all animals. At necropsy, macroscopic examination of main organs showed no abnormalities. Adverse dermal reactions noted were slight to moderate erythema and edema, which completely recovered to normal within four days.

The acute dermal LD50 of nopyl acetate was therefore higher than 2000 mg/kg bw under the test conditions.

Acute oral and dermal toxicity studies indicated limited toxicological effects at 2000 mg/kg bw.


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

Justification for selection of acute toxicity – inhalation endpoint
Acute toxicity is already assessed by two different routes of exposure (oral and dermal routes), that showed very low toxicity, with high LD50 values.
Moreover, the vapour pressure of Nopyl acetate (1.33 Pa at 20°C) indicates low volatility. Therefore, no exposure by inhalation is expected and in accordance with column 2 of REACH Annex VIII (section 8.5), the acute toxicity by inhalation does not need to be conducted.

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

Justification for classification or non-classification

Oral and dermal LD50 are higher than 2000 mg/kg bw in mice and rabbits, respectively, therefore nopyl acetate is not classified for acute toxicity according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.