Registration Dossier

Administrative data

Description of key information

Oral
Rat: LD50 > 2000mg/kg (BASF SE 2011 acc. to OECD 423 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: Japan MAFF 8147
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
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: app. 10 weeks
- Weight at study initiation: 170 - 190g
- Fasting period before study: 16h (water available ad lib.)
- Housing: single in Macrolon type III cages
- 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: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h/12h
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.82mL/kg b.w.
Doses:
2000mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of administration, daily thereafter on workdays
- Frequency of weighing: before administration and weekly thereafter, additionally at the day of death of the animal that died on study day 1
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 1 of 6 animals died
Mortality:
one female died on day one
Clinical signs:
One animal did not show any clinical signs.
Impaired general state, dyspnoea and piloerection were observed in two animals at hour 4 and 5. Ataxia was observed in these animals at hour 5. Either of them was found dead on study day 1.
Beginning with hour 1 or 2, impaired general state, dyspnoea and piloerection was noted until hour 5 in three animals. In one of these animals these clinical signs persisted until study day 3, while ataxia was noted in this animal at hour 5 only.
Body weight:
The mean body weight of the test groups increased throughout the study period within the normal range with the exception of one female of the first administration group, which showed reduction of body weight during the first post-exposure week, but gained adequately weight during the second post-exposure week.
Gross pathology:
There were no macroscopic pathological findings in the five females sacrificed at the end of the observation period.
In the animal that died on study day 1 the following findings were observed at necropsy:
stomach filled with liquid content, extensive bleeding in the glandular stomach; partly black discolored spleen (one-third), red discoloration of content in small intestine, red discolored small intestine and congestion in the kidneys.
Interpretation of results:
relatively harmless
Remarks:
Migrated information
Conclusions:
The acute oral LD50 in rats was found to be greater than 2000mg/kg b.w. in female rats.
Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class method, 2000 mg/kg bw of the undiluted test item were administered to two test groups of three fasted Wistar rats by gavage. The following test item-related clinical observations were recorded during the course of the study:

· One out of six animals died

· Impaired general state

· Dyspnoea

· Piloerection

· Ataxia

· The mean body weight of the animals increased within the normal range throughout the study period with the exception of one female of the first administration group, which showed reduction of body weight during the first post-exposure week, but gained adequately weight during the second postexposure week.

The following macroscopic pathological findings were recorded in the animal that died:

· Stomach: filled with liquid content

· Glandular stomach: extensive bleeding

· Spleen: black discoloration in one-third

· Small intestine: red discoloration

· Content of the small intestine: red discoloration

· Kidneys: congestion

· There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period (5 females).

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
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:
adopted Feb. 1987
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
adopted May 2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
adopted August 1998
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan no. 8147
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
- 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 228 - 237g, females: 209-211g
- Fasting period before study: no
- Housing: single in makrolon cages, 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: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 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
- Type of wrap if used: semi-occlusive

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.82ml/kg b.w.

Duration of exposure:
24h
Doses:
2000mg/kg
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: several times on the day of exposure, at least once daily on each workday thereafter
- Frequency of weighing: shortly before administration, weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, scoring of skin findings (30-60min after exposure, several times thereafter)
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality occured
Clinical signs:
no systemic clinical signs were observed. For local irritation, see table 1 (males) and table 2 (females)
Body weight:
normal increase
Gross pathology:
no abnormalities noted

Table 1:

Nature and duration of local clinical signs(males)
Dose (mg/kg bw): 2000
Sex: male
Administration: 1
No. of animals: 5
Animal No.: R 954 R 955 R 956 R 957 R 958
Abnormalities:          
Erythema grade 1: d9 - d12 d7 - d9 d13 d6 - d9 d8 - d9
Erythema grade 2: d1 - d2;
d7 - d8
d1 - d2; d6 d1 - d2;
d9 - d12
d1 - d5 d1 - d2; d7
Erythema grade 3: d5 - d6 d5 d5 - d8 - d5 - d6
Edema grade 1: - d1 - d2 d1 - d2 d1 - d2 d1 - d2
Incrustations: d5 - d8 d5 - d6 d5 - d12 - d5 - d8
Scaling: d5 - d 13 d5 - d7; d9 d5 - d14 d5 - d8 d5 - d9
Sever scaling: - d8 - - -
Skin findings beyond the
application area:
- - d6 - d13 - -
Significant scratching
behavior
d2 - d6 d2 - d5 d2 - d6 d2 - d5 d2 - d6

d: day

Table 2:

Nature and duration of local clinical signs(females)
Dose (mg/kg bw): 2000
Sex: female
Administration: 1
No. of animals: 5
Animal No.: R 959 R 960 R 961 R 962 R 963
Abnormalities:          
Erythema grade 1: d12 - d13 d14 d12 - d13 d12 - d13 d14
Erythema grade 2: d1 - d2;
d8 - d9
d1 - d2;
d12 - d13
d1 - d2;
d7 - d9
d1 - d2 d1 - d2;
d12 - d13
Erythema grade 3: d5 - d7 d5 - d9 d5 - d6 d5 - d9 d5 - d9
Edema grade 1: d6 - d9 - - d6 -
Edema grade 2: - - - d5 -
Incrustations: d5 - d12 d5 - d14 d5 - d12 d5 - d14 d5 - d14
Scaling: d5 - d14 d5 - d14 d5 - d9 d5 - d14 d5 - d14
Skin findings beyond the
application area:
- d6 - d14 d6 - d9 d6 - d14 d6 - d14
Significant scratching
behavior
d1 - d5 d1 - d5 d2 d2 - d3 d1 - d5
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
Under the conditions of this study the median lethal dose (LD50) of the test material 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 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. The following test item-related local effects were recorded during the course of the study:

· No mortality occurred

· No signs of systemic toxicity were observed in the animals

· Slight to moderate erythema (grade 1 to 3)

· Slight to well-defined edema (grade 1 to 2)

· Incrustations

· Scaling

· Severe scaling

· Skin findings beyond the application area

· Significant scratching behavior

· The mean body weight of the animals increased within the normal range throughout the study period

· 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 OECD 423 and GLP (BASF SE 2011), 2 groups of 3 female fasted Wistar rats each were given a single oral dose of 2000mg/kg of undiluted test substance by gavage. The animals were observerd for 14 days and a necropsy was performed. One animal died on day one. Necropsy revealed liquid content in the stomach, extensive bleeding in the glandular stomach, partly black discolored spleen, red discoloration of content in the small intestine, red discolored small intestine and congestion in the kidneys. No pathological findings were observed in the 5 surving rats at the end of the observation period. The expected body weight gain has been observed in the course 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 animals increased within the normal range throughout the study period. 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:

- Slight to moderate erythema (grade 1 to 3)

· Slight to well-defined edema (grade 1 to 2)

· Incrustations

· Scaling

· Severe scaling

· Skin findings beyond the application area

· Significant scratching behavior

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, (5 -ethyl-1,3 -dioxan-5 -yl) methyl acrylate is not required to be classified for its acute toxicity potential according to 67/548/EEC and CLP/EU-GHS requirements.