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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Read across justification: The target chemical belongs to the homologues series of alkyl ether nitrile, where there is an incremental increase in the number of CH2 units. Therefore, it can be assumed that target and source chemicals share the same toxic mode action.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
3-(isodecyloxy)propiononitrile
EC Number:
264-840-1
EC Name:
3-(isodecyloxy)propiononitrile
Cas Number:
64354-92-3
IUPAC Name:
3-[(8-methylnonyl)oxy]propanenitrile

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: Wistar rat

Strain: Hoe: WISKf(SPF71)

Origin: Hoechst Aktiengesellschaft, Kastengrund ; SPF breeding colony

Body weight at start of study
male animals
mean = 178g (= 100 %)
s = ±7g
min = 167g (- 6.2 %)
max = 184g (+ 3.4 %)
n = 5
female animals
mean = 176g (= 100 %)
s = ±5g
min = 172g (- 2.3 %)
max = 184g (+ 4.5 %)
n = 5

Age at the start of the study: male animals approximately 7 weeks ; female animals approximately 8 weeks

Randomization: Randomization schemes 95.0650 and 96.0193

Animal maintenance: in fully air-conditioned rooms in macrolon cages (type 4) on soft wood granulate in groups of 5 animals

Room temperature: 22 ±3°C

Relative humidity: 50±20%

Lighting time: 12 hours daily

Acclimatization: at least one day (breeding at identical conditions)

Food: ssniff'ID R/M-H (V 1534), ad libitum

Withdrawal of food: from about 16 hours before to 3 - 4 hours after treatment

Water: tap water in plastic bottles. ad libitum

Animal identification: fur marking with KMnO. and cage numbering















Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
The animals received the compound as a 20 % solution in sesame oil (Oleum sesami Ph. Eur. III, Fa. Mainland Pharmazeutische Fabrik GmbH), the application volume being 10 ml/kg body weight.
Doses:
2000mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The prepared test substance was administered by gavage to fasted animals at the stated dosage (2000mg/kg bw). The observation period following treatment lasted for 14 days. Symptoms were recorded twice every day (in the moming and in the afternoon), on weekends and public holidays only once. During this time the animals were weighed weekly. At the end of the observation period the animals were killed by carbon dioxide asphyxiation, dissected and examined for macroscopically visible changes.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the whole study.
Clinical signs:
The following clinical signs were observed after the application of Isodeeylethernitril:
decreased spontaneous activity, sunken flanks, squatting posture, bristled coat, stupor, stilted gait, uneoordinated or ataxie gait, prone position, irregular respiration and inereased respiration rate. At day three of the study all clinical signs were reversible.
Body weight:
Development of body weight was not impaired.
Gross pathology:
The animals killed at the end of the observation period showed no macroseopically visible changes.

Any other information on results incl. tables

The analogue approach using 3-(isodecyloxy)propiononitrile as source chemical is justified:

a.   The target chemical belongs to the homologues series ofalkyl ether nitrile, where there is an incremental increase in the number of CH2 units. Therefore, it can be assumed that target and source chemicals share the same toxic mode action.

b.   The findings using in-silico tool DEREK are comparable for target and source chemicals. Toxicological concerns of hepatotoxicity are identified with a likelihood of equivocal based on the aliphatic nitrile structure of both target and source chemicals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No classification is warranted for the target substance based on the analogue approach using isodecylethernitril as read-across supporting substance. Acute oral toxicity testing of Isodecylethemitril in the Wistar rat yielded a median lethal dose (LC50) above 2000 mg/kg body weight in both male and female animals.
Executive summary:

The acute oral toxicity of the target substance was assessed based on the read-across appoach using isodecylethernitril as read-across supporting substance.

Acute oral toxicity testing of Isodecylethemitril in the Wistar rat yielded a median lethal dose (LC50) above 2000 mg/kg body weight in both male and female animals. No lethality occurred after application of 2000 mg/kg body weight. Beside unspecific clinical signs the animals showed impairments of respiration as weil as motility, stupor and prone position. At day three of the study all c1inical signs were reversible. Oevelopment of body weight was not impaired. The animals killed at the end of the observation period showed no macroscopically visible changes.

No classification is warranted for the target substance based on the analogue approach.