1-Octanol, reaction products with epichlorohydrin and 2-mercaptoethanol

Endpoint summary

Description of key information

The oral LD50 is greater than 2000 mg/kg. 
The acute dermal median lethal dose (LDS0) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

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:

2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: according to EC Directive 92/69/EEC and Regulation EC/440/2008 guideline methods under GLP conditions

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

acute toxic class method

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were identified by cage notation and indelible body marks, and housed in suspended wire mesh cages; 5/sex/cage prior to dosing and 3/sex/cage following dosing. Bedding was placed beneath the cages and changed at least three times/week. Fresh PMI Rat Chow (Diet #5012) was freely available except for 16-20 hours prior to dosing. Water was freely available at all times. The animal room, reserved exclusively for rats on acute tests, was temperature controlled, had a 12 hour light/dark cycle, and was kept clean and vermin free.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

syringe and dosing needle gavage/feed

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 male and 3 female rats

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All three males and all three females survived the 2000 mg/kg oral dose.

Clinical signs:

other: None

Other findings:

Necropsy results were normal.
Instances of dyspnea, noted in one animal, were the only pysical signs noted during the study.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: US CPSC / US OSHA

Conclusions:

This substance is considered to be in Acute Toxic Class 0. The LD50 is greater than 2000 mg/kg.

Executive summary:

This substance is considered to be in Acute Toxic Class 0. The LD50 is greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Study done according to EC Directive 92/69/EEC and Regulation EC/440/2008 guideline methods under GLP conditions. Klimisch rating = 1.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study done according to EC Directive 92/69/EEC and Regulation EC/440/2008 guideline methods under GLP conditions. Klimisch rating = 1.

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

Group 1:
Mean achieved atmosphere concentration: 0.90 mg/L
Mean mass median aerodynamic diameter (MMAD): 1.54 µm
Deaths: 0/3 male, 0/3 female.

Group 2:
Mean achieved atmosphere concentration: 4.73 mg/L
Mean mass median aerodynamic diameter (MMAD): 2.06 µm
Deaths: 1/3 male, 2/3 female.

Analytical verification of test atmosphere concentrations:

yes

Concentrations:

0.90 mg/L
4.73 mg/L

No. of animals per sex per dose:

3 males and 3 females per dose

Control animals:

no

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4.73 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Sex:

male/female

Dose descriptor:

LC0

Effect level:

0.9 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No deaths in the 0,90 mg/L group.

Deaths: 1/3 male, 2/3 female in the 4,73 mg/L group. These animals were humanely killed due to the severity of the observations noted, these animals were considered unlikely to survive.

Clinical signs:

other: Common abnormalities noted during the study included increased respiratory rate or decreased respiratory rate, labored respiration, noisy respiration, hunched posture, pilo-erection, red/brown staining around the snout and wet fur. There were frequent ins

Body weight:

Group 1 - All animals exhibited body weight losses on Day 1 post-exposure. With the exeption of one female which showed a further body weight loss from Days 1 to 3 post-exposure, all animals exhibited body weight gains during the remainder of the recovery period.
Group 2 - All animals exhibited body weight loss on Day 1 post-exposure. All surviving animals exhibited further body weight losses from Days 1 to 3. Body weight gains were noted for all surviving animals during the remainder of the recovery period.

Gross pathology:

No macroscopic abnormalities were detected amongst animals from Group 1 or from the surviving animals from Group 2.
The following macroscopic abnormalities were detected at necropsy in the animals from Group 2 that were humanely killed during the course of the study at necropsy:
Lungs: abnormally pale or pale patches;
Liver: dark;
Kidneys: dark;
Stomach - gaseous distention;
Small Intestine: gaseous distension;
Large Intestine: gaseous distension.
Due to the observations noted it is considered that the deaths noted during the study may have been mainly attributable to local toxicity.

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No animals died in a group of six rats exposed to a mean achieved atmosphere concentration of 0.90 mg/L, where as three deaths occured at the mean achieved atmosphere concentration of 4.73 mg/L. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC59) of Dynol 360, in the RccHan(TM): WIST strain rat, was in the range >1-5 mg/L (Globally Harmonized Classification System - Category 4) and had a 4 hr LC50 cut-off value of 5 mg/L.

LC50 is found to be at 4,73 mg/m³ (4,73 µg/L) of mist in a acute toxicity test according to OECD guideline 436: Acute Inhalation Toxicity – Acute Toxic Class Method. Hence the test substance is classified as toxic category IV according to CLP.

Executive summary:

LC50 is found to be at 4,73 mg/m³ (4,73 µg/L) of mist in a acute toxicity test according to OECD guideline 436: Acute Inhalation Toxicity – Acute Toxic Class Method. Hence the test substance is classified as toxic category IV according to CLP.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

4 mg/m³ air

Quality of whole database:

Study done according to EC Directive 92/69/EEC and Regulation EC/440/2008 guideline methods under GLP conditions. Klimisch rating = 1.

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:

2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: according to EC Directive 92/69/EEC and Regulation EC/440/2008 guideline methods under GLP conditions

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Method: A group of ten animals (five males and five females) was given a single, 24-hour, semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.
Five male and five female Sprague-Dawley CD (Crl: CD" (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd, Margate, Kent, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals weighed at least 200g, and were eight to twelve weeks of age. The weight variation did not exceed +/- 20% of the mean weight for each sex.
The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food (Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations fiom these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:OO to 18:OO h) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day before treatment the back and flanks of each animal were clipped free of hair.
The calculated volume of test material, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The animals were caged individually for the 24-hour exposure period.
Shortly after dosing the dressings were examined to ensure that they were securely in place.
After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.
The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.

After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31:

Duration of exposure:

24 h

Doses:

Dose Level: 2000 mg/kg
Specific Gravity: 1.005
Dose Volume: 2.00 ml/kg

No. of animals per sex per dose:

5 male and 5 female rats

Control animals:

not required

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Other findings:

No abnormalities were noted at necropsy.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Study done according to EC Directive 92/69/EEC and Regulation EC/440/2008 guideline methods under GLP conditions. Klimisch rating = 1.

Additional information

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

Justification for selection of acute toxicity – inhalation endpoint
Only study available.

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

Justification for classification or non-classification

According to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Part 3 classification required.

According to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Part 3 Chapter 3.1 classification is required, since this substance causes concern of acute inhalation toxicity. It is classified to be acute toxic to inhalation Category 4. LC50 1 -5 mg/m³ for aerosols and particulates. No classification for the oral and dermal route required.