Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Acute Oral Toxicity (weight of evidence): LD50 > 2000 and < 5000 mg/kg bw, 2019

1. Acute Oral (Read-Across: 4-methyl-2-phenyltetrahydro-2H-pyran): LD50 > 2000 mg/kg bw, eq. or similar to EU Method B.1, 1992

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:
1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
inspected: June 1990 ; signature: September 1990
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD(SD)BR strain (VAF plus)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: 4-6 weeks
- Weight at study initiation: males 100-113g; females 109 - 116g
- Fasting period before study: overnight before dosing
- Housing: Animals were housed in groups of 5, by sex, in grid bottomed cages suspended over cardboard lined excreta trays. cardboard tray liners were changed as often as necessary to maintain hygiene.
- Diet (e.g. ad libitum): pelleted diet ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 32-52
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hour dark / 12 hours light
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 per sex dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were examined shortly after dosing and approximately 30 minutes, 1, 2 and 4 hours after dosing and daily thereafter for 14 consecutive days. On the day of dosing all animals were weighed in order to calculate the amount of test article to be administered. They were weighed again on day 8 and on day 15.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One female was euthanasied on day 2 as death was considered to be inevitable. The remaining animals survived to the end of the study.
Clinical signs:
other: A hunched posture was seen in all females and most males from day 1, but by day 3 all surviving animals appeared to be outwardly healthy.
Gross pathology:
No significant findings that are not consistent with background macroscopic pathology of the strain.
Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test substance in male and female Crl:CD(SD)BR strain (VAF plus) of rat was estimated to be greater than 2000 mg/kg body weight.
Executive summary:

The study was performed according to a method equivalent to EU Method B.1 and/or OECD TG 401 guidelines in accordance with GLP. The test material was administered as a single oral dose, by gavage, at a dose level of 2000 mg/kg bodyweight to a group of 5 male and 5 female rats following an overnight fast. The animals were observed for 14 days and survivors were then euthanized. All animals were subject to necropsy. One female was humanely euthanized as death was considered to be inevitable; all remaining animals survived to the end of the study. Clinical signs of toxicity were noted in most animals on the day of dosing, but all surviving animals appeared outwardly healthy from day 3 onwards. There was no adverse effect on bodyweight gain in animals of either sex. Necropsy findings were of low incidence and are considered not to be significant. When administered as a single oral dose of 2000 mg/ kg bodyweight, the test material produced some evidence of toxicity in the rat. The LD50 for both sexes combined is estimated to be in excess of 2000 mg/kg.

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included in attachment to IUCLID section 13.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across is based on the hypothesis that the source and target substances have common structural features in the same relative positions. The source and target have similar physico-chemical, toxicological properties and because of common metabolism they share common or have similar breakdown products and therefore potential mechanisms of action. Further information is included in attachment to IUCLID section 13.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source and target chemicals have comparable chemical similarity. Further information is included in attachment to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
The source substance is a chemically similar substance with common metabolism and common or similar degradants of the target substance. Further information is included in attachment to IUCLID section 13

4. DATA MATRIX
Further information is included in attachment to IUCLID section 13.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
inspected: June 1990 ; signature: September 1990
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD(SD)BR strain (VAF plus)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: 4-6 weeks
- Weight at study initiation: males 100-113g; females 109 - 116g
- Fasting period before study: overnight before dosing
- Housing: Animals were housed in groups of 5, by sex, in grid bottomed cages suspended over cardboard lined excreta trays. cardboard tray liners were changed as often as necessary to maintain hygiene.
- Diet (e.g. ad libitum): pelleted diet ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 32-52
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hour dark / 12 hours light
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 per sex dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were examined shortly after dosing and approximately 30 minutes, 1, 2 and 4 hours after dosing and daily thereafter for 14 consecutive days. On the day of dosing all animals were weighed in order to calculate the amount of test article to be administered. They were weighed again on day 8 and on day 15.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One female was euthanasied on day 2 as death was considered to be inevitable. The remaining animals survived to the end of the study.
Clinical signs:
other: A hunched posture was seen in all females and most males from day 1, but by day 3 all surviving animals appeared to be outwardly healthy.
Gross pathology:
No significant findings that are not consistent with background macroscopic pathology of the strain.
Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The target substance acute oral median lethal dose (LD50) in male and female Crl:CD(SD)BR strain (VAF plus) of rat is expected to be greater than 2000 mg/kg body weight.
Executive summary:

The study was performed on a source substance according to a method equivalent to EU Method B.1 and/or OECD TG 401 guidelines in accordance with GLP. The test material was administered as a single oral dose, by gavage, at a dose level of 2000 mg/kg bodyweight to a group of 5 male and 5 female rats following an overnight fast. The animals were observed for 14 days and survivors were then euthanized. All animals were subject to necropsy. One female was humanely euthanized as death was considered to be inevitable; all remaining animals survived to the end of the study. Clinical signs of toxicity were noted in most animals on the day of dosing, but all surviving animals appeared outwardly healthy from day 3 onwards. There was no adverse effect on bodyweight gain in animals of either sex. Necropsy findings were of low incidence and are considered not to be significant. When administered as a single oral dose of 2000 mg/ kg bodyweight, the test material produced some evidence of toxicity in the rat. The LD50 for both sexes combined is estimated to be in excess of 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute Oral Toxicity:

1. Eq. to EU Method B.1, 1992 : Read-Across - SOURCE (4-methyl-2-phenyltetrahydro-2H-pyran): The study was performed according to a method equivalent to EU Method B.1 and/or OECD TG 401 guidelines in accordance with GLP. The test material was administered as a single oral dose, by gavage, at a dose level of 2000 mg/kg bodyweight to a group of 5 male and 5 female rats following an overnight fast. The animals were observed for 14 days and survivors were then euthanized. All animals were subject to necropsy. One female was humanely euthanized as death was considered to be inevitable; all remaining animals survived to the end of the study. Clinical signs of toxicity were noted in most animals on the day of dosing, but all surviving animals appeared outwardly healthy from day 3 onwards. There was no adverse effect on bodyweight gain in animals of either sex. Necropsy findings were of low incidence and are considered not to be significant. When administered as a single oral dose of 2000 mg/ kg bodyweight, the test material produced some evidence of toxicity in the rat. The LD50 for both sexes combined is estimated to be in excess of 2000 mg/kg.

Justification for classification or non-classification

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity.

 

The weight of evidence based on read-across to analogue substances; via the oral route indicates that the substance cannot be expected to produce acute toxicity sufficient for classification and labelling under the EU criteria at category 4 levels. The substance would be expected to be classified in GHS category 5 levels with an expected LD50 of > 2000 and < 5000 mg/kg bw.