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Description of key information

Acute oral toxicity: The LD50 for male and female rats was greater than 2000 mg/kg bw.

Acute dermal toxicity: A LD50 value of > 2000 mg/kg bw was determined for the test substance.

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:
key study
Study period:
from 1990-09-06 to 1990-09-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
February 24, 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
Directive 84/449/EEC, September 19, 1984
Deviations:
no
GLP compliance:
yes
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Strain: SPF-bred Wistar rats (strain Bor: WISW (SPF Cpb)
- Age at study initiation: young-adult. At the start of the experiment, male rats were about 7 weeks old and females 10 weeks, based on their body weights.
- Weight at study initiation: The mean initial weight of males and females were 173 g and 167 g, respectively. The mean deviation in animal weights was less than 20 %.
- Housing: The rats were housed in groups of 5 animals each, under conventional conditions, in Makrolon type III cages on low-dust wood granules
- Nutrition: The animals received fixed-formula standard diet Altromin® 1324 pellets and tap water ad libitum. There were feeding troughs fitted in the cage lids as feed containers. Water was offered in polycarbonate bottles holding approximately 700 mL. The nutritional composition and the contaminant content of the standard diet were routinely spot-checked and analysed. The tap water was of drinking quality. The results of the feed and water analyses have been filed. The data available produced no evidence of any influence on the study objective.
From approximately 16 hours prior to application up to 4 hours thereafter feed was withdrawn, all the other time it was available ad libitum. Tap water was available ad libitum during the entire study period.
- Acclimation period: at least 4 days.
- Other: Females were nulliparous and not pregnant. The condition of the animals' health was checked before the start of experiment. Only healthy animals, without any clinical signs, were included in the study.

ENVIRONMENTAL CONDITIONS
- Temperature: room temperature (22 ± 2 °C)
- Humidity: about 50 ± 10 %
- Air changes: approximately ten air changes per hour
- Photoperiod: 12-hour light/dark cycle (artificial light from 6 a.m. to 6 p.m. CET)
- Other: All animals of this study were kept in one animal room. For reasons of capacity, animals from other toxicological studies were temporarily housed in the same animal room. Mixing up of the animals or mutual influence was avoided by appropriate organisation of the operations.

IN-LIFE DATES: From: 1990-09-06 To: 1990-09-20
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Remarks:
1,2-propanediol
Details on oral exposure:
DOSE VOLUME APPLIED:
Application volume of 10 mL/kg bw
Doses:
Rationale for the selection of the dose:
According to OECD Guideline 401 of Feb. 24, 1987, sufficient assessment of acute oral toxicity is achieved as a rule, even if no substance related lethality occurs at a dose of 2000 mg/kg body weight. The following dose was administered: 2000 mg/kg body weight.
No. of animals per sex per dose:
5 male and 5 female animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: before administration (day 0), after one week and at the end of the 14-day observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None of the animals died during the 14-day observation period.
Clinical signs:
All males and one female showed rough coat as a sign of intoxication after single administration of 2000 mg/kg. Two males additionally displayed increased salivation and apathy. The signs appeared approximately half an hour after the application, were of slight-to moderate intensity and persisted up to 24 hours after the treatment.
Body weight:
Growth of the animals was not affected.
Gross pathology:
Necropsy findings: The animals sacrificed at the end of study did not show any noticeable gross pathological findings.
The following signs of intoxication were observed: rough coat, increased salivation and apathy.
Other findings:
- Analytical investigations:
The analytical investigations into the stability of the test compound showed that it was stable for the duration of use in the concentration range employed.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for male and female rats was greater than 2000 mg/kg bw.
Executive summary:

Acute toxicological investigations with male and female Wistar rats were conducted after oral administration (gavage) of the test substance in accordance with OECD guideline 401. The LD50 for male and female rats was determined to be greater than 2000 mg/kg bw and was not exactly determined. The following signs of intoxication were observed: rough coat, increased salivation and apathy. The body weight development of male and female rats was not affected. No animal died during the 14-day observation period. None of the animals sacrificed at the end of study showed any unusual gross pathological features.


 

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
from 1978-05-29 to 1978-05-29
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
No details on experimantal conditions, GLP and guidelines available.
Principles of method if other than guideline:
The test item was administered once orally by gavage to 10 male Wistar rats. The animals were observed for the following 14 days for mortality and clinical signs.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen (SPF)
- Strain: Wistar TNO W 74
- Age at study initiation: ca. 9 weeks
- Average weight at study initiation: 199 g
- Housing: Makrolon cages type III, dust-free granulate made of wood
- Diet: Altromin R 1324 (Source: Altromin GmbH, Lage), ad libitum
- Water: drinking water, ad libitum
-Number of animals: 5 animals per group

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 1.5 °C
- Humidity: ca. 60 ± 5 %
- Photoperiod: 12 h artificial illumination (7:00 am to 7:00 pm)
Route of administration:
oral: gavage
Vehicle:
other: luterol
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5 animals
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the entire study period.
Clinical signs:
increased diureasis
Interpretation of results:
study cannot be used for classification
Conclusions:
The LD50 for male rats was determined to be greater than 5 g/kg bw.
Executive summary:

Acute toxicological investigations with male Wistar rats were conducted after oral administration (gavage) of the test substance formulated in luterol. The LD50 for male was determined to be greater than 5 g/kg bw and was not exactly determined. The following signs of intoxication were observed: increased diuresis. No animal died during the 14-day observation period.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

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:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Justification for type of information:
According to REACH Regulation (EC) No 1907/2006, Annex VIII, 8.5 data for a maximum of two routes of exposure need to be provided. Testing for acute toxicity via the inhalation route was not applicable as data on acute oral and acute dermal toxicity were available. Furthermore, as the vapour pressure is very low, exposure to Incozol EH is, therefore, unlikely, so the acute toxicity via inhalation was also waived for animal welfare reasons.
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:
from 1992-04-15 to1992-04-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
Directive 84/449/EWG, 19.09.1984
Deviations:
no
GLP compliance:
yes
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain: Bor: WISW (SPF Cpb)
- Source: Winkelmann, Borchen
- Age at study initiation: ca. 10 weeks (males), ca. 16 weeks (females)
- Weight at study initiation: ca. 244 g (males), 221 g (females)
- Housing: conventional Makrolon cages type II, dust-free granulate (wood).
- Diet: "fixed-formula" standard diet (altromin 1324 pellets, source: Altromin GmbH und Co KG, Lage) ad libitum
- Water: drinking water ad libitum in 300 mL flasks made of poly carbonate
- Acclimation period: 5 days
- Other: Female animals were nullipara and non-pregnant. Health of the animals was checked before study initiation. Only healthy animals without any symptoms were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 50 ± 10 %
- Air changes: ca. 10 changes per hour
- Photoperiod: 12 h illumination (6:00 am to 6:00 pm)
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flank
- % coverage: ca. 10 % of body surface
- Preparation of test site: The test site was clipped ca. 24 hours before application. The skin was not hurt.
- Patches (Fermoflex tape, Baiersdorf AG) and aluminium foil was used for coverage of the test site.

REMOVAL OF TEST SUBSTANCE
- Washing: lukewarm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Concentration: 100 %
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 female animals and 5 male animals
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
On day 1 of the application and during the 14-day observation period the animals were inspected twice a day (on weekend and holyday once a day) regarding clinical signs and, if necessary, dead animals were removed. Immediately before the application (day 1), after 1 week and at the end of the 14-day observation period the animals were weighted. The calculation of the individual application volume was calculated on the basis of the body weight recorded before study initiation.
- Necropsy of survivors performed: yes, using diethyl ether
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
During the 14-day observation period no mortality was observed.
Clinical signs:
Systemic symptoms of poisoning and local changes on the skin were not observed.
Body weight:
The growth of male rats was not influenced. Female animals showed a temporarily decrease or stagnation of their body weight.
Gross pathology:
All animals that were sacrificed at the end of the study did not show any conspicuous symptoms.
Interpretation of results:
GHS criteria not met
Conclusions:
A LD50 value of >2000 mg/kg bw was determined for the test substance.
Executive summary:

The test substance was examined for its acute dermal toxicity similar to EU method B.3. Ten Wistar rats were equally divided to sex. A dose of 2000 mg/kg bw was applied. The hair was clipped from the back of each animal, the test substance was applied for 24 hours and the application site was covered with patches and aluminium foil. After an observation time of 14 days no mortality was observed. The growth of male rats was not influenced. Female animals showed a temporarily decrease or stagnation of their body weight. Systemic symptoms of poisoning and local changes on the skin were not observed. All animals that were sacrificed at the end of the study did not show any conspicuous symptoms. Thus, the deduced LD50 value is >2000 mg/kg bw.


 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Acute toxicity: oral


Key study:


Acute toxicological investigations with male and female Wistar rats were conducted after oral administration (gavage) of the test substance in accordance with OECD guideline 401. The LD50 for male and female rats was determined to be greater than 2000 mg/kg bw and was not exactly determined. The following signs of intoxication were observed: rough coat, increased salivation and apathy. The body weight development of male and female rats was not affected. No animal died during the 14-day observation period. None of the animals sacrificed at the end of study showed any unusual gross pathological features.


Supporting study:


Acute toxicological investigations with male Wistar rats were conducted after oral administration (gavage) of the test substance formulated in luterol. The LD50 for male was determined to be greater than 5 g/kg bw and was not exactly determined. The following signs of intoxication were observed: increased diuresis. No animal died during the 14-day observation period.


 


Acute toxicity: inhalation


According to REACH Regulation (EC) No 1907/2006, Annex VIII, 8.5 data for a maximum of two routes of exposure need to be provided. Testing for acute toxicity via the inhalation route was not applicable as data on acute oral and acute dermal toxicity were available. Furthermore, as the vapour pressure is very low exposure to Incozol EH is therefore unlikely, so the acute toxicity via inhalation was waived also for animal welfare reasons.


 


Acute toxicity: dermal


The test substance was examined for its acute dermal toxicity similar to EU method B.3. Ten Wistar rats were equally divided to sex. A dose of 2000 mg/kg bw was applied. The hair was clipped from the back of each animal, the test substance was applied for 24 hours and the application site was covered with patches and aluminium foil. After an observation time of 14 days no mortality was observed. The growth of male rats was not influenced. Female animals showed a temporarily decrease or stagnation of their body weight. Systemic symptoms of poisoning and local changes on the skin were not observed. All animals that were sacrificed at the end of the study did not show any conspicuous symptoms. Thus, the deduced LD50 values is >2000 mg/kg bw.

Justification for classification or non-classification

Based on the available data the test item is not classified for acute oral, dermal and inhalation toxicity according to Regulation (EC) No 1272/2008, as amended for the 17th time in Regulation (EU) 2021/849.