Registration Dossier

Administrative data

Description of key information

LD50 oral: > 2000 mg/kg bw
LD50 dermal: > 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: comparable to guideline study
Qualifier:
according to
Guideline:
other: Richtlinie 84/449/EWG, test protocol corresponds to OECD 401, Limit Test
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan-Winkelmann, Borchen, Germany
- Acclimation period: at least 5 days
- Age at study initiation: males appr. 7-8 weeks, females appr. 9-10 weeks
- Fasting period before treatment: 16 hours
- Fasting period after treatment: 4 hours
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no data
- Volume of application: 10 ml/kg bw

The test substance was
Doses:
2000 mg/kg bw
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: twice daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
limit test, no statistics required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: clinical signs: temporarily increased salivation and breathing sounds which disappeared up to day 3 after treatment
Mortality:
none; one male died immediately after dosing as a consequence of misapplication of the test substance
Clinical signs:
temporarily increased salivation and breathing sounds which disappeared up to day 3 after treatment
Body weight:
not influenced by treatment
Gross pathology:
no unusual lesions were noted; yellowish liquid was observed in the male which was died by misapplication
Executive summary:

The acute oral toxicity of the test item was evaluated in a GLP-compliant study on male and female Wistar rats. The acute oral LD50 was determined with > 2000 mg/kg bw. As clinical signs temporarily increased salivation and breathing sounds were observed which disappeared up to day 3 after treatment.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The study is GLP compliant and has Klimisch score 1.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: HsdCpb: Wu
- Source: Harlan GmbH, 5960 AD Horst, Netherlands
- Age at study initiation: approximately 9-13 weeks
- Diet and water: ad libitum
- Acclimation period: at least 5 days
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
One day before the start of the treatment the back and flanks of the rats were shorn (approximately 10 % of the body surface area). For each dose and animal the required amount of the pure liquid test substance was calculated on the base of the body weight at time of dosing. This amount was weighed and applied as uniformly and thinly as possible to the test area, covered with a gauze-layer (6.0 cm x 5.0 cm = 30.0 cm²) of a "Cutiplast steril" coated with "Leukoflex". The gauze strip was placed on the rat's back and secured with a "Lomir biomedical Inc rat jacket", which was connected with a safety pin to the stretch tape to ensure that the animals could not ingest the test substance.

REMOVAL OF TEST SUBSTANCE
After approximately 24 hours the dressings were removed and the area was rinsed with tepid water using soap and gently patting the area dry.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw per 30.0 cm²
Dose range: males 18.9 - 19.5 mg/cm²; females 14.6 - 15.7 mg/cm².
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: at least 14 days
- Frequency of observations and weighing: Clinical signs and mortality rates were determined several times on the day of application and subsequently at least once daily. The weight gain of the animals was checked weekly until the end of the study.
- Necropsy of survivors performed: yes
Statistics:
none; limit dose study; judgement according to the Globally Harmonization System (GHS) in analogy with the OECD Draft Guideline 434.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no clinical signs, no effects on weight development and no gross pathological findings; local effects: partial reddening of the treatment area in one male and one female
Mortality:
No mortalities occured.
Clinical signs:
No clinical signs were observed.
Body weight:
There were no toxicologically significant effects on body weight or body weight development in males and females.
Gross pathology:
The necropsies performed at the end of the study revealed no particular findings.
Other findings:
partial reddening of the treatment area in one male (day 2) and one female (day 2-3) animal
Executive summary:

An acute dermal toxicity study (limit test) was performed on male and female rats according to OECD TG 402. No mortalities, clinical signs, effects on body weight or gross pathological findings were observed during the 14 -day observation period. Local effects became obvious as partial reddening of the skin in one male and one female rat. The resulting dermal LD50 was > 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The study is GLP compliant and has Klimisch score 1.

Additional information

Desmorapid 01 can be chemically described as ‘butanoic acid, 3-oxo-, methylester, reaction products with N,N-dimethyl-1,3-propanediamine and propylene glycol ether with trimethylol propane (3:1) (CAS-No. 646505-36-4)’ or (different description of the same substance) ‘poly [oxy(methyl-1,2-ethanediyl)] , a -hydro-w -hydroxy-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol (3:1), 3-[[3-dimethylamino) propyl]imino]butanoate’ (CAS-No. 857285-61-1). The closely related CAS-No. 179733-18-7 describes the same substance and differs only in the manufacturing process where ethanol is distilled off while for the other two CAS-Nos. methanol is distilled off (see IUCLID section 1.1). Thus, toxicological data for all three CAS-Nos. are considered relevant for the substance to be registered and are taken into account for human health assessment.

Acute oral toxicity

The acute oral toxicity of the test item (CAS-No. 179733 -18 -7) was evaluated in a GLP-compliant study on male and female Wistar rats. The acute oral LD50 was determined with > 2000 mg/kg bw. As clinical signs temporarily increased salivation and breathing sounds were observed which disappeared up to day 3 after treatment.

Acute dermal toxicity

An acute dermal toxicity study (limit test) was performed on male and female rats according to OECD TG 402 with the test item (CAS-No. 646505 -36 -4). No mortalities, clinical signs, effects on body weight or gross pathological findings were observed during the 14 -day observation period. Local effects became obvious as partial reddening of the skin in one male and one female rat. The resulting dermal LD50 was > 2000 mg/kg bw.

Acute inhalation toxicity

Acute inhalation toxicity studies are not available for the substance.


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

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

Justification for classification or non-classification

The acute oral and dermal toxicity was proven to be low with LD50 values of > 2000 mg/kg. Thus, no classification with regard to acute oral and dermal toxicity is required.