Registration Dossier

Administrative data

Description of key information

Oral
Rat: LD50 >2000mg/kg (BASF AG 1993, acc. to EU method B1 and GLP)
Dermal
Rat: LD50 > 2000mg/kg (BASF SE 2011 acc. to OECD 402 and GLP)

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:
1992/93
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach
- Age at study initiation: young adult
- Weight at study initiation: 178-190g
- Fasting period before study: 16h (water available ad lib.)
- Housing: single, in stainless steel wire mesh cages, type DK-III
- Diet (e.g. ad libitum): Kliba-lab-diet 343, ad lib.
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: > 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h/12h

Route of administration:
oral: gavage
Vehicle:
olive oil
Remarks:
DAB 9
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 40g/100ml
- Justification for choice of vehicle: poor solubility of test substance in water

MAXIMUM DOSE VOLUME APPLIED: 5ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no acute toxicity expected due to chemical characteristics
Doses:
2000mg/kg
No. of animals per sex per dose:
3 males + 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
observations: several times on the day of administration, thereafter: twice daily on workdays, daily on weekends
body weight: day 0, weekly thereafter and at the end of the study before the fasting period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
none
Body weight:
expected gain
Gross pathology:
no findings
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
Under the conditions of this study the median lethal dose after oral applications was found to be greater than 2000mg/kg b.w. for the male and female animals.
Executive summary:

The study was preformed to assess the range of mortality following oral administration of the test material, applied as a solution in olive oil DAB 9, to Wistar rats.

A group of 6 fasted animals (3males and 3females) was given a single oral dose of test material preparation in olive oil DAB 9 at a dose level of 2000mg/kg body weight.

Signs of toxicity have not been noted.

The expected body weight gain has been observed in the course of the study.

No mortality occured.

No abnormalities were noted at necropsy of animals sacrificed at the end of the study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
10/2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
other: Wistar / Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: males: app. 8 weeks, females: app. 12 weeks
- Weight at study initiation: males: 242-296g, females: 204-220g
- Fasting period before study: no
- Housing: single in Makrolon cage, type III
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany ad lib.
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: >= 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h/12h

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: app. 40cm² (corresponds to at least 10% of body surface)
- fur clipped: 24h prior to application (dorsal and dorsolateral parts of the trunk)
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze) and stretch bandage (Fixomull® Stretch)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, using warm water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.86ml/kg b.w.
- Concentration (if solution): undiluted

Duration of exposure:
24h
Doses:
2000mg/kg b.w.
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 and weighing:
observations: several times on the day of application, at least once daily thereafter on each workday
skin findings: 30-60 minutes after removal of the semi-occlusive dressing, several times until last day of observation
body weight: on day 0 prior to application, weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology, local skin reactions
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortatlity
Mortality:
no
Clinical signs:
male and female: no systemic effects
male - local effects:
In three males slight erythema (grade 1) was observed on study day 1 and 2. Well-defined erythema (grade 2) was observed in the two other animals on study day 1 and 2 after application. In these two animals slight edema (grade 1) was observed on study day 1 only.
female - local effects:
In three females slight erythema (grade 1) was observed on study day 1 which increased to well-defined erythema (grade 2) on study day 2. In one of these animals this grade was noted until study day 5 but decreased again to slight (grade 1) on study day 6. Additionally incrustations were observed in this animal from study day 5 until study day 7. In one animal well-defined erythema was observed from study day 1 until study day 6 which decreased to slight erythema on study day 7 and persisted until study day 9 after application. Slight edema (grade 1) was observed in this female animal from study day 1 until study day 5. In addition, incrustations (from study day 2) and scaling (from study day 5) were noted until study day 9 in this animal. Well-defined erythema was observed in the fifth animal on study day 1 and 2 after application. In this animal slight edema (grade 1) was observed on study day 1.
Body weight:
The mean body weight of the male animals increased within the normal range throughout the study period.
The mean body weights of the female animals did not significantly change during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range.
Gross pathology:
no findings
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
Under the conditions of this study the median lethal dose (LD50) of the test substance after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.
Executive summary:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days.

· No signs of systemic toxicity were observed in the animals.

· The following test item-related local effects were recorded during the course of the study:

o Slight to well-defined erythema (grade 1 to 2)

o Very slight edema (grade 1)

o Incrustations

o Scaling

· The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weights of the female animals did not significantly change during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range.

· No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

In an acute oral toxicity study (Limit test) according to EU method B1 and GLP (BASF AG 1993), 3 male and 3 female fasted Wistar rats were given a single oral dose of 2000mg/kg in olive oil DAB 9 by gavage. The animals were observerd for 14 days and a necropsy was performed. No mortality occured and no signs of toxicity have not been noted. The expected body weight gain has been observed in the course of the study. No abnormalities were noted at necropsy of animals sacrificed at the end of the study. Thus the oral LD50 value for this substance is greater than 2000mg/kg b.w.

In an acute dermal toxicity study (Limit Test) according to OECD 402 and GLP (BASF SE 2011), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No signs of systemic toxicity were observed in the animals. The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weights of the female animals did not significantly change during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. The following test item-related local effects were recorded during the course of the study:

o Slight to well-defined erythema (grade 1 to 2)

o Very slight edema (grade 1)

o Incrustations

o Scaling

Since no deaths occured, the dermal LD50 is greater than 2000mg/kg b.w.

In accordance with column 2 of REACH Annex VIII, no acute inhalation toxicity study was conducted as two other routes are provided. But it is stressed, that due to the high reactivity of the substance, aerosols should not be inhaled.

Justification for classification or non-classification

Based on the results of the available studies, Propylidynetrimethanol, ethoxylated, esters with acrylic acid, reaction products with 1-Butanamine, N-butyl- is not required to be classified for its acute toxicity potential according to 67/548/EEC and CLP/EU-GHS requirements.