Registration Dossier

Administrative data

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:
other: 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.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Name of the test item (as cited in the study report): Nopyl Acetate
Source: Proprietary Perfumes Ltd.
Date received: 04 February 1977
Colour: Clear colourless
Specific gravity: 0.98
pH: 4.5

Test animals

Species:
mouse
Strain:
not specified
Sex:
male/female
Details on test animals 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

Administration / exposure

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

Results and discussion

Preliminary study:
not applicable
Effect levels
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:
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 somnolent and the females dosed at 5 and 10 mL/kg bw were comatose. Within 2 h 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.
Body weight:
Surviving animals gained weight during the 7 day observation period and presented a normal appearance at autopsy.
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

Any other information on results incl. tables

none

Applicant's summary and conclusion

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.