Fatty acids, tall-oil, reaction products with bisphenol A, epichlorohydrin, glycidyl tolyl ether and triethylenetetramine

Endpoint summary

Description of key information

The acute median lethal oral dose level of the test article, TOFA_TETA_PAA_BADGE_CGE_Adduct, was found to exceed 2000 mg/kg.
The acute median lethal dermal dose of TOFA_TETA_PAA_BADGE_CGE_Adduct to rats was found to exceed 2000 mg/kg.

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:

18 September 2012 to 25 March 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Fully GLP compliant and in accordance with current test guidelines

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

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:

other: HsdHan:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester
- Age at study initiation: 11 to 12 weeks
- Weight at study initiation: The weight variation did not exceed ±20% of the mean weight.
- Fasting period before study: fasting from the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing
- Housing: The animals were housed in groups of up to five during the acclimatisation period in cages that conform to the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989). From the day prior to dosing (Day –1), the rats were housed in groups of three in similar cages.
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1, ad libitum
- Water (e.g. ad libitum): Mains water, ad libitum
- Acclimation period: 28 to 30 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 45 to 65%
- Air changes (per hr): The animal rooms were designed to permit 15 to 20 air changes per hour.
- Photoperiod (hrs dark / hrs light): The rooms were illuminated by fluorescent strip-lights for twelve hours daily.

IN-LIFE DATES: From: 15 October 2012 To: 01 November 2012

Route of administration:

oral: gavage

Vehicle:

other: PEG 400

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 100 mg/mL
- Amount of vehicle (if gavage): 20 mL/kg
- Justification for choice of vehicle: The test article was dispersed in PEG 400 as this was found to produce a suitable formulation at the highest concentration.
- Lot/batch no. (if required): Not reported
- Purity: Not reported

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

No. of animals per sex per dose:

3 animals per group. 6 per dose level

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:Clinical signs were recorded immediately after the first administration and at approximately 15 and 30 minutes after first administration. Clinical signs were then recorded immediately after the second administration, at approximately 15 and 30 minutes after the second, hourly between 1 and 4 hours after the second administration (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period.
Rats were weighed on Day -1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight

Statistics:

Not applicable

Sex:

female

Dose descriptor:

discriminating dose

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No clinical signs were seen.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The acute median lethal oral dose level of the test article, TOFA_TETA_PAA_BADGE_CGE_Adduct, was found to exceed 2000 mg/kg.
The test material was considered to have no significant acute toxic risk in respect of its acute oral toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Executive summary:

This study was conducted to assess the acute toxicity of the test article, TOFA_TETA_PAA_BADGE_CGE_Adduct following oral administration to rats.

Groups of three female fasted rats were given the test article on Day 1 by oral gavage at a dose level of 2000 mg/kg. The test article was dispersed in PEG 400 at a concentration of 100 mg/mL and administered at a dose volume of 10 mL/kg on two occasions approximately one hour apart. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths and no clinical signs were seen.

All rats achieved body weight gains during the study period.

No abnormalities were noted at necropsy.

The acute median lethal oral dose level of the test article, TOFA_TETA_PAA_BADGE_CGE_Adduct, was found to exceed 2000 mg/kg.

The test material was considered to have no significant acute toxic risk in respect of its acute oral toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

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:

18 September 2012 to 25 March 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Fully GLP compliant and in accordance with current test guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: HsdHan:WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 248 to 286 g (males) and 173 to 199 g (females)
- Fasting period before study: Not applicable
- Housing: During the acclimatisation period, up to five rats of the same sex were accommodated in cages that conformed to the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989). From the day prior to dosing (Day –1), each rat was individually housed in a similar cage. After completion of the Day 3 observations animals allocated to the main study were returned to group housing.
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1, ad libitum
- Water (e.g. ad libitum): Mains water, ad libitum
- Acclimation period: 7 to 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 45 to 65%
- Air changes (per hr): The animal rooms were designed to permit 15 to 20 air changes per hour.
- Photoperiod (hrs dark / hrs light): The rooms were illuminated by fluorescent strip-lights for twelve hours daily.

IN-LIFE DATES: From: 01 October 2012 To: 23 October 2012

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsum
- % coverage: 10%
- Type of wrap if used: Dense gauze patch retained in place by an elasicated, open-weave adhesive compression bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dermal test site of each rat was lightly brushed clean of any solid residues and swabbed with water-moistened cotton wool
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): Not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: Not applicable

Duration of exposure:

15 Days

Doses:

1 dose at 2000 mg/kg

No. of animals per sex per dose:

five male and five female rats was subjected to single dermal application of the test article at 2000 mg/kg. This group consisted of the two animals used in the preliminary test plus a further four male and four female rats to give the required group size of five males and five females.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Clinical signs were recorded immediately post dose, at approximately 15 and 30 minutes post dose, hourly between 1 and 4 hours post dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. Individual records of clinical signs were maintained for each treated rat.
Rats were weighed on Day -1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal reactions, necropsy findings

Statistics:

Not applicable

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no clinical signs of reaction to treatment.

Gross pathology:

Abnormalities noted at necropsy were confined to a sore appearance of the skin at the treatment site.

Other findings:

No evidence of oedema was noted during the study period.
Very slight to well-defined erythema was noted in all males on Day 2. Very slight erythema persisted in one male to the end of the study and was also noted in one other male on Days 5 and 6.
Very slight erythema was noted in all females on Day 2. Very slight erythema was noted in one female on Days 3 and 4, with very slight to well-defined erythema noted in all females on Days 5, 6 and 7. Very slight erythema persisted in four females up to Day 14 and in one female on Day 15.
Other adverse dermal reactions noted were brown discolouration of the skin, shiny skin and scabbing.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The acute median lethal dermal dose of TOFA_TETA_PAA_BADGE_CGE_Adduct to rats was found to exceed 2000 mg/kg.
The test material was considered to have no significant acute toxic risk in respect of its acute dermal toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Executive summary:

This study was conducted to determine the acute dermal toxicity of the test article, TOFA_TETA_PAA_BADGE_CGE_Adduct following a single (24 hour) semi-occluded topical application to the rat.

The test article was applied as an undiluted liquid to the clipped dorsum of a group of five male and five female rats on Day 1. Each rat received a single topical application at a dose level of 2000 mg/kg. The treated areas of dorsum were covered by a semi-occlusive dressing for 24 hours. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths and no clinical signs of reaction to treatment.

Adverse dermal reactions noted were very slight to well-defined erythema, brown discolouration of the skin, shiny skin and scabbing.

One female showed no change in body weight during the first week of the study and another female showed a slight loss in body weight during the second week. All other rats gained weight during the first and second weeks of the study.

Abnormalities noted at necropsy were confined to a sore appearance of the skin at the treatment site.

The acute median lethal dermal dose of TOFA_TETA_PAA_BADGE_CGE_Adduct to rats was found to exceed 2000 mg/kg.

The test material was considered to have no significant acute toxic risk in respect of its acute dermal toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Acute Oral Toxicity

A study according to OECD 423 was conducted to assess the acute toxicity of the test article, TOFA_TETA_PAA_BADGE_CGE_Adduct following oral administration to rats.

Groups of three female fasted rats were given the test article on Day 1 by oral gavage at a dose level of 2000 mg/kg. The test article was dispersed in PEG 400 at a concentration of 100 mg/mL and administered at a dose volume of 10 mL/kg on two occasions approximately one hour apart. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths and no clinical signs were seen. All rats achieved body weight gains during the study period. No abnormalities were noted at necropsy.

The acute median lethal oral dose level of the test article, TOFA_TETA_PAA_BADGE_CGE_Adduct, was found to exceed 2000 mg/kg.

The test material was considered to have no significant acute toxic risk in respect of its acute oral toxicity.

Acute Dermal Toxicity

An OECD 402 study (limit test) was conducted to determine the acute dermal toxicity of the test article, TOFA_TETA_PAA_BADGE_CGE_Adduct following a single (24 hour) semi-occluded topical application to the rat.

The test article was applied as an undiluted liquid to the clipped dorsum of a group of five male and five female rats on Day 1. Each rat received a single topical application at a dose level of 2000 mg/kg. The treated areas of dorsum were covered by a semi-occlusive dressing for 24 hours. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths and no clinical signs of reaction to treatment. Adverse dermal reactions noted were very slight to well-defined erythema, brown discolouration of the skin, shiny skin and scabbing. One female showed no change in body weight during the first week of the study and another female showed a slight loss in body weight during the second week. All other rats gained weight during the first and second weeks of the study. Abnormalities noted at necropsy were confined to a sore appearance of the skin at the treatment site.

The acute median lethal dermal dose of TOFA_TETA_PAA_BADGE_CGE_Adduct to rats was found to exceed 2000 mg/kg.

The test material was considered to have no significant acute toxic risk in respect of its acute dermal toxicity.

Acute Inhalative Toxicity

Considering the low vapour pressure of the test substance inhalative exposure is unlikely and has not been tested.

Justification for selection of acute toxicity – oral endpoint
Only study available for this endpoint

Justification for selection of acute toxicity – dermal endpoint
Only study available for this endpoint

Justification for classification or non-classification

The test material was considered to have no significant acute toxic risk in respect of its acute oral and dermal toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) respectively CLP (Regulation EC No 1272/2008) or DSD (Directive 67/548/EEC).

Data on acute inhalative toxicity are not available and not required as inhalative exposure is unlikely due to the low vapour pressure of the substance. No effect triggering classification for STOT SE classification according to GHS/CLP were noted in the available studies and hence classification for short term specific target organ toxicity is not required.