Reaction products of Soya and Linseed Oil Fatty Acids with Bisphenol A diglycidylether

Endpoint summary

Description of key information

oral LD50 >5000 mg/kg bw (rat, OECD TG 423)

dermal LD50 >2000 mg/kg bw (rat, OECD TG 402)

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:

13 December 2018 - 18 April 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study was performed in accordance with the OECD Principles of Good Laboratory Practice as accepted by Regulatory Authorities throughout the European Union, United States of America (FDA and EPA), Japan (MHLW, MAFF and METI) and other countries that are signatories to the OECD Mutual Acceptance of Data Agreement.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

Test System:
Condition: Outbred, SPF-Quality
Source: Charles River Deutschland, Sulzfeld, Germany
nulliparous and non-pregnant
Age at the Initiation of Dosing: Young adult animals (approximately 10 weeks old)
Fasting period before study: overnight fast immediately before dosing and for approximately 3 to 4
hours after dosing
- Housing: in groups of up to 3 in suspended solid floor polycarbonate cages containing sterilized sawdust as bedding material
- Diet: SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany; ad libitum throughout the study, except for the period of overnight prior to dosing and until 3-4 hrs post dose administration
- Water: Municipal tap-water was freely available to each animal via water bottles
- Acclimation period: at least 5 days

Environmental Conditions
Temperature range: 20 to 21°C
Relative Humity range: daily mean relative humidity of 27 to 53%
12-hour light/12-hour dark cycle
Ten or greater air changes per hour with 100% fresh air (no air recirculation)

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

two consecutive groups of three female Wistar Han rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: CLinical Observations at 0, 2 and 4 hr after dosing on day 1 and then once daily. Morbidity and mortality checks were made twice daily, early and late during normal working
days, and once daily at weekends and public holidays.
Frequency of weighing: Days 1 (predose), 8 and 15
days, and once daily at weekends and public holidays.
- Necropsy of survivors performed: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mL/kg bw

Based on:

test mat.

Mortality:

No unscheduled deaths

Clinical signs:

other: Hunched posture and piloerection were noted for the animals on Days 1 and/or 2

Gross pathology:

No Abnormalities

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of Soya/Linseed Oil Fatty Acid-BADGE reaction product in Wistar Han rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Executive summary:

The objective of this study was to assess the toxicity of the test item when administered in a single dose to female rats at one or more defined dosages. The study was carried out in compliance with the guidelines described in:

 OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method".

 EC No 440/2008, part B: "Acute Oral Toxicity, Acute Toxic Class Method".

 EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity".

 JMAFF Guidelines (2000), including the most recent revisions.

Soya/Linseed Oil Fatty Acid-BADGE reaction product was administered by oral gavage to

two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight. Animals

were subjected to daily observations and weekly determination of body weight. Macroscopic

examination was performed after terminal sacrifice (Day 15).

No mortality occurred.

Hunched posture and piloerection were noted for the animals on Days 1 and/or 2.

The body weight gain shown by the animals over the study period was considered to be

similar to that expected for normal untreated animals of the same age and strain.

No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of Soya/Linseed Oil Fatty Acid-BADGE reaction product in Wistar Han

rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed

5000 mg/kg body weight.

Based on these results, Soya/Linseed Oil Fatty Acid-BADGE reaction product does not have

to be classified and has no obligatory labelling requirement for acute oral toxicity according

to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of

the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on

classification, labelling and packaging of items and mixtures (including all amendments).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

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:

13 December 2018 - 17 April 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

2017

Deviations:

yes

Remarks:

Temporary deviations from the minimum level of target humidity occurred for 3 days (minimum of 36%)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Batch: F288I1K351

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Age at study initiation: 9-11 weeks
- Weight at study initiation: 165 - 207g
- Fasting period before study: no
- Housing: 1 per polycarbonate cage containing sterilized sawdust
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum
- Water (e.g. ad libitum): Municipal tap-water was freely available to each animal via water bottles
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 21°C
- Humidity (%): 36 to 53
- Air changes (per hr): 10 or more
- Photoperiod (hrs dark / hrs light): 12-hour dark/12-hour light cycle

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

One day before dosing, an area of approximately 5x7 cm on the back of the animals was clipped. The test item was applied in an area of approximately 10% of the total
body surface, i.e. approximately 25 cm² for males and 18 cm² for females. The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D),
successively covered with Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

Duration of exposure:

24 hr

Doses:

2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 0, 2, and 4 hrs after dose adminstration and then once daily thereafter
Frequency of weighing: Day 1, 8, and 15
- Necropsy of survivors performed: yes
-

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mL/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: No irritation was noted for any of the animals at any time point. No clinical signs were noted.

Gross pathology:

No Abnormalities

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 value of Soya/Linseed Oil Fatty Acid-BADGE reaction product in Wistar Han rats was established to exceed 2000 mg/kg body weight.

Executive summary:

The objective of this study was to determine the potential toxicity of Soya/Linseed Oil Fatty Acid-BADGE reaction product, when given by a single dermal dose.

The study was carried out based on the guideline described in:

 OECD No. 402 (2017) "Acute Dermal Toxicity".

Initially, Soya/Linseed Oil Fatty Acid-BADGE reaction product was administered to 3 female Wistar Han rats by a single dermal application at 2000 mg/kg body weight for 24 hours

All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

No mortality occurred and no clinical signs were noted. No skin reactions were noted during the observation period. Overall, the body weight gain shown by the surviving animals during the observation period

was considered not indicative of toxicity.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of Soya/Linseed Oil Fatty Acid-BADGE reaction product in Wistar Han rats was established to exceed 2000 mg/kg body weight.

Based on these results, Soya/Linseed Oil Fatty Acid-BADGE reaction product does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity

according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No

1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity

Soya/Linseed Oil Fatty Acid-BADGE reaction product was administered by oral gavage to two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred.

Hunched posture and piloerection were noted for the animals on Days 1 and/or 2.

The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of Soya/Linseed Oil Fatty Acid-BADGE reaction product in Wistar Han rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results, Soya/Linseed Oil Fatty Acid-BADGE reaction product does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

 

Acute inhalation toxicity

The study does not need to be conducted, because exposure of humans via inhalation is not likely taking into account the vapour pressure and the exposure to aerosols or droplets.

 

Acute dermal toxicity

Soya/Linseed Oil Fatty Acid-BADGE reaction product was administered to 3 female Wistar Han rats by a single dermal application at 2000 mg/kg body weight for 24 hours.

All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

No mortality occurred and no clinical signs were noted. No skin reactions were noted during the observation period. Overall, the body weight gain shown by the surviving animals during the observation period was considered not indicative of toxicity.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of Soya/Linseed Oil Fatty Acid-BADGE reaction product in Wistar Han rats was established to exceed 2000 mg/kg body weight.

Based on these results, Soya/Linseed Oil Fatty Acid-BADGE reaction product does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

 

 

Based on the available information, the acute toxicity of Soya/Linseed Oil Fatty Acid-BADGE reaction product is low. There are no data gaps in acute toxicity. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.

Justification for classification or non-classification

The oral and dermal LD50 of Soya/Linseed Oil Fatty Acid-BADGE reaction product was assessed to be > 2000 mg/kg bw. According to GHS Regulation EC No 1272/2008 no classification and labelling for acute toxicity is necessary.