Phenol, paraalkylation products with C12-rich branched olefins derived from propene oligomerisation, reaction products with sulphur monochloride and decene, reaction products with Benzoic acid, 2-hydroxy-,C14-18 alkyl dervis., polybutenyl benzenesulphonic acid, carbon dioxide and calcium hydroxide

Endpoint summary

Description of key information

The acute oral LD50 is >2000 mg/kg bw.
The acute dermal LD50 is >2730 mg/kg bw (Read Across).

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:

31 January to 16 February 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Compliant with GLP and OECD test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK, Margate
- Age at study initiation: approximately 8 to 10 weeks old
- Weight at study initiation: between 200 and 230 g
- Fasting period before study: overnight before dosing
- Housing: Groups of 3
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approximately 22°C on each day
- Humidity (%): approximately 32% to 47%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: To: 31 January to 16 February 2012

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 500 mg/mL
- Amount of vehicle (if gavage): Not recorded
- Justification for choice of vehicle: Formulation trial at Charles River Laboratories
- Lot/batch no. (if required): MKBG9425V
- Purity: Not recorded

MAXIMUM DOSE VOLUME APPLIED: 4 mL/kg

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Review of the Sponsor's MSDS indicated LD50 >5000 mg/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

2 groups of 3 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least 5 times on the day of dosing and once daily thereafter, until Day 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights

Statistics:

None

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no unscheduled deaths during the study.

Clinical signs:

other: No adverse clinical signs were recorded in any animal.

Gross pathology:

No macroscopic abnormalities were recorded in any animal.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study the median lethal dose level (LD50) of EC 903 162 9 in Sprague-Dawley rats was considered to exceed 2000 mg/kg.
This study is considered to be relevant, reliable and adequate for risk assessment and for classification purposes.

Executive summary:

The objective of this OECD 423 study was to assess the adverse effects which can follow within a short period of time after a single oral gavage administration of EC 903-162-9 to rats. The test item was administered to 2 groups, each comprising 3 female Sprague-Dawley rats, at a dose level of 2000 mg/kg. The animals were observed for 14 days after the day of dosing. The test item was formulated in corn oil. The dose volume, 4 mL/kg, was based on the concentration of the test formulation (500 mg/mL). Individual doses were based on each individual animal’s body weight on the day of dosing. The following parameters and end points were evaluated in this study: clinical signs, body weights, body weight changes, and gross necropsy findings.

All animals survived treatment and no adverse clinical signs or macroscopic abnormalities were recorded in any animal. Body weight gains were considered to be acceptable for rats of this age and strain. Under the conditions of the study the median lethal dose level (LD50) of EC 903-162-9 in Sprague-Dawley rats were considered to not exceed 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 1 study conducted in accordance with OECD guidelines and GLP.

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:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

31 January to 21 February 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study on analogue substance conducted to GLP and OECD test guideline.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK, Margate
- Age at study initiation: 8 to 10 weeks old
- Weight at study initiation: 202 and 236 g (males) and 199 and 250 g (females)
- Fasting period before study: Not applicable
- Housing: Singly
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Approximately 22°C on each day
- Humidity (%): Approximately 32% to 49%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hrs dark, 12 hrs light

IN-LIFE DATES: From: To: 31 January to 21 February 2012

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: ~21 cm2 (males) and ~38 cm2 (females)
- % coverage: ~7% (males) and ~12% (females)
- Type of wrap if used: Micropore and Sleek tape

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.44 mL (males) and 0.45 mL (females)
- Concentration (if solution): NA
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2370 mg/kg (The selected dose level for this study was 2000 mg/kg. The Sponsor stated that the test item density was
1.185 kg/L. Because the density was not used to calculate the administered dose volumes, the actual dose
level was 2370 mg/kg).

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: At least 5 times on the day of dosing and once daily from Day 2 to Day 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 370 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths among animals treated with EC-903-161-3 at 2370 mg/kg.

Clinical signs:

other: There were no signs of systemic toxicity in any animal at any observation timepoint. Clinical signs were restricted to test item residues at the test site, which was seen in all animals on Day 2 only.

Gross pathology:

There were no abnormal findings noted at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the median lethal dermal dosage (LD50) for EC-903-161-3 in Sprague-Dawley rats was estimated to be greater than 2370 mg/kg. This study is considered to be relevant, reliable and adequate for risk assessment and for classification purposes for EC 903-162-9.

Executive summary:

The objective of this OECD 402 study was to assess the adverse effects which can follow within a short period of time after a single dermal administration of EC-903-161-3 to rats.

The test item was administered to a single group of 5 male and 5 female Sprague-Dawley rats. The study design was as follows:

Text Table1
Experimental Design

Dose Level (mg/kg)	Dose Volume (mL/kg)	Animal Numbers
		Males	Females
2370	2	1 to 5	6 to 10

 

The selected dose level for this study was 2000 mg/kg. The Sponsor stated that the test item density was 1.185 kg/L. Because the density was not used to calculate the administered dose volumes, the actual dose level was 2370 mg/kg.

 

The test item was administered, as supplied, onto the dorsal trunk under a gauze patch which was covered with semi-occlusive tape, then secured with occlusive tape (iethe site was fully occluded). The dressings remained in place for 24 h. The dose was calculated on the basis of the body weights of the animals on the day of dosing. Animals were observed for signs of reaction to treatment a minimum of 5 times on the day of dosing. Thereafter animals were observed once daily from Day 2 until the end of the observation period on Day 15. Body weights were recorded weekly and all animals were subjected to a necropsy examination.

The following parameters and end points were evaluated in this study: clinical signs, body weights, body weight changes, and gross necropsy findings.

There were no unscheduled deaths during the observation period.

There were no systemic signs of toxicity noted in any animal at any observation timepoint and local findings at the dosing site were restricted to test item residues at the test site, which was seen in all animals on Day 2 only.

Body weight gain was considered to be acceptable for rats of this age and strain. No abnormal findings were noted at necropsy.

Under the conditions of the study, the median lethal dermal dosage (LD₅₀) for EC-903-161-3 in Sprague-Dawley rats was estimated to be greater than 2370 mg/kg.

The study is being used as read across from EC 903-161-3 to EC 903-162-9. The justification for this read across is provided in IUCLID section 13.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 370 mg/kg bw

Quality of whole database:

Klimisch 2 study (due to it being on a read-across substance) conducted in accordance with OECD guidelines and GLP.

Additional information

Acute toxicity oral

A limit test study conducted in accordance with the OECD 423 guideline reported that there were no deaths following a single oral dose of test article among rats dosed at 2000 mg/kg. No adverse clinical signs or macroscopic abnormalities were recorded in any animal and

no signs of systemic toxicity were noted during the study. The acute median lethal oral dose was found to exceed 2000 mg/kg, therefore the test material was considered to have no significant acute toxic risk if swallowed.

Acute toxicity dermal

A limit test study conducted in accordance with the OECD 402 guideline reported that there were no unscheduled deaths during the observation period following a single dermal administration of test article onto the dorsal trunk under a gauze patch among rats dosed at 2370 mg/kg. There were no systemic signs of toxicity noted in any animal at any observation time point and local findings at the dosing site were restricted to test item residues at the test site, which was seen in all animals on Day 2 only. The acute median lethal dermal dose was found to exceed 2370 mg/kg, therefore the test material was considered to have no significant acute toxic risk if in contact with skin. The acute dermal study is read across from material EC 903-161-3. The justification for use of this read across is detailed in IUCLID section 13. It is considered the LD50 of >2370 mg/kg bw for EC 903-161-3 is also representative of that of EC 903-162-9.

Acute toxicity inhalation

In accordance with Rule 8.5 of Annex VIII of the REACH Regulation, a study of the acute inhalation toxicity is not required, since studies of acute toxicity via oral exposure and via dermal exposure have been provided. Furthermore, the potential for inhalation exposure to occur is considered negligible.

Justification for selection of acute toxicity – oral endpoint
Key study conducted in accordance with OECD guideline 423 and GLP.

Justification for selection of acute toxicity – dermal endpoint
Read across of study conducted in accordance with OECD guideline 402 and GLP on an analogue substance. Justification for suitability for read across is provided in IUCLID section 13.

Justification for classification or non-classification

Acute Toxicity Oral

The acute oral LD50 is >2,000 mg/kg bw, therefore no classification for acute oral toxicity is required according to regulation (EC) 1272/2008 (CLP).

Acute Toxicity Dermal

An acute dermal LD50 value of >2,370 mg/kg bw was recorded in a relevant read across study (justification for read across is presented in IUCLID section 13), therefore no classification for acute dermal toxicity is required according to regulation (EC) 1272/2008 (CLP).

Acute Toxicity Inhalation

No acute inhalation toxicity data are available. Based on the low acute toxicity via both the oral and dermal routes of exposure, no classification for acute inhalation toxicity is proposed.

Specific Target Organ Toxicity - Single Exposure

No adverse clinical signs or macroscopic abnormalities were recorded in any animal, there were no remarkable bodyweight changes. Consequently, no classification for Single Exposure Specific Target Organ Toxicity is required under regulation (EC) 1272/2008 (CLP)