Linseed oil, ester with pentaerythritol

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Reference 1

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

no

GLP compliance:

yes

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeding centre Charles River Deutchland, Sulzfeld, Germany)
- Age at study initiation: 6 weeks
- Housing: in group of five in Macrolon cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9-22.0 deg. C
- Humidity (%): 31-84%
- Air changes (per hr): 15times/h
- Photoperiod (hrs dark / hrs light): 12 h dark / 12 h light

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: accuracy of the diet preparations ranged from 87% to 95% of nominal value, which was considered as an acceptable level of accuracy

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Chemical analyses revealed that experimental diets were homogenously prepared; accuracy of the diet ranged from 87%-95% of nominal value

Duration of treatment / exposure:

98 and 100 days for female and male rats, respectively

Frequency of treatment:

Daily

Remarks:

Doses / Concentrations:
0%
Basis:
nominal in diet

Remarks:

Doses / Concentrations:
1%
Basis:
nominal in diet

Remarks:

Doses / Concentrations:
5%
Basis:
nominal in diet

Remarks:

Doses / Concentrations:
15%
Basis:
nominal in diet

No. of animals per sex per dose:

10

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: No higher dose level than 15% was selected as nonspecific effects of high fat intake in rats can be expected to appear at dose levels above 15%

Positive control:

None

Observations and examinations performed and frequency:

All animals were observed twice daily for mortality/viability and at least once daily for clinical observations and signs for toxicity, feed intake and body weight were evaluated once a week

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

None

Statistics:

Where the variables were assessed to follow a normal distribution, a Dunnett-test based on a pooled variance estimate, was applied to compare the treated groups and the control group of each gender. The Steel-test was applied where the data could not be assumed to follow a normal distribution. The exact Fishertest was applied to frequency data. All tests were two-sided and in all cases p < 0.05 was accepted as the lowest level of significance. Group means were calculated for continuous data.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

no effects observed

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

no effects observed

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not examined

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

HAEMATOLOGY: Statistically significant changes in haematology parameters were considered to be of no
toxicological relevance as they occurred in the absence of a dose related response and/or were of a very slight size. These changes included lower white blood cell counts (WBC) and protrombin times in males fed 15% KPNO, higher relative neutrophil and lower relative lymphocyte count in females fed 1% and 5% KPNO but not in females of the 15% KPNO dose group, and lower haemoglobin and haematocrit levels in females fed 1% KPNO but not in females fed 5% or 10% KPNO in the diet.

CLINICAL CHEMISTRY: Higher alkaline phosphatase activity levels (ALP) in females fed 15% KPNO, lower total bilirubin levels in males fed 5% and 15% KPNO, lower total protein levels in females fed 1%, 5% and 15% KPNO, lower cholesterol levels in males fed 15%, and in females fed 1%, and 15% KPNO, lower calcium levels in males and females fed 1%, 5% and 15% KPNO, lower inorganic phosphate levels in males fed 15% and increased creatinine and sodium levels in the females of 5% KPNO group. Although some statistical significant changes in biochemical parameters were observed it is important to note that compared to rats on a normal fat diet, most changes fall within the historical control values.


URINALYSIS


NEUROBEHAVIOUR


ORGAN WEIGHTS

Key result

Dose descriptor:

NOAEL

Effect level:

8 866 mg/kg bw/day (nominal)

Sex:

male

Basis for effect level:

other: see 'Remark'

Key result

Dose descriptor:

NOAEL

Effect level:

10 242 mg/kg bw/day (actual dose received)

Sex:

female

Basis for effect level:

other: see 'Remark'

Key result

Critical effects observed:

not specified

Conclusions:

Under the study conditions, the NOAEL for subchronic oral toxicity was determined to be 8866 and 10242 mg/kg bw/day for male and female rats, respectively.

Executive summary:

A study was conducted to determine the subchronic oral toxicity of glycerides, C16-18 and C18-unsatd. (in the form of pine nut oil) according to OECD Guideline 408, in compliance with GLP. The test substance was administered through the diet to three groups, each of ten male and ten female Wistar Crl:Wi(Han) strain rats, for up to 98 and 100 consecutive days, at dose levels of 0, 1, 5 and 15% per day. In Week 12, a functional observation test was carried out. At Week 13, ophthalmoscopic examinations were conducted. Clinical signs, bodyweight development, food intake and mortality/viability were monitored during the study. Haematology and blood chemistry were evaluated for all animals at the end of the treatment period. All animals were subjected to gross necropsy and macroscopic examination and a complete histopathological examination was performed. No toxicological significant changes were observed. Under the study conditions, the NOAEL for subchronic oral toxicity was determined to be 8866 and 10242 mg/kg bw/day for male and female rats, respectively (Gerrit, 2009).

Reference 2

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

From November 1992, to December 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Specific details on test material used for the study:

Form: Liquid

Species:

rat

Strain:

other: Alpk:APfSD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Zeneca Pharmaceuticals, Alderly Park, Macclesfield, Cheshire, UK
- Age at study initiation: 28 d
- Weight at study initiation: 148.45 g (males); 122.6 g (females)
- Housing: sexes separately, five per cage, cages had measurements of 26.5 x 50.0 x 20.0 cm and were constructed of stainless steel mesh with one solid side.
- Diet: CT1 diet; Special Diets Services Limited, Witham, Essex, UK, ad libitum
- Water: tap water, ad libitum
- Acclimation period: approx. 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23°C
- Humidity (%): 45 - 65 (71 at one occasion)
- Air changes (per hr): 25 - 30
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: November 1992 To: December 1992

Route of administration:

oral: feed

Vehicle:

other: in diet

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: All diet preparations were based on CT1 diet (Special Diets Services Limited, Witham, Essex, UK). They were prepared by grinding the appropriate amount of test substance with 1 kg of milled CT1 diet. This premix was then added to 14 kg of diet and mixed thoroughly with a Pharma Blender Model PMA 100S (T K Filder).

DIET PREPARATION
- Rate of preparation of diet (frequency): 15 kg batches
- Mixing appropriate amounts with (Type of food): CT1 diet (Special Diets Services Limited, Witham, Essex, UK)
- Storage temperature of food: - 20°C, stored at room temperature for usage up to 14 days

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Chemical stability was determined for diet preparations over a period of 5 weeks following storage at room temperatureT or at -20°C. Samples were extracted by chemical shaking with ethyl acetate. The supernatant was diluted with ethyl acetate to give solutions containing appropriate concentrations of the test substance. Extracts were analysed by gas chromatography using flame ionisation detection. The extract concentration was calculated by reference to data from a standard containing a known concentration.

Duration of treatment / exposure:

daily

Frequency of treatment:

28 d

Dose / conc.:

1 000 ppm

Remarks:

Corresponding to 112 and 119 mg/kg bw/day for males and females, respectively

Dose / conc.:

5 000 ppm

Remarks:

Corresponding to 562 and 586 mg/kg bw/day for males and females, respectively

Dose / conc.:

12 500 ppm

Remarks:

Corresponding to 1450 and 1613 mg/kg bw/day for males and females, respectively

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Dose selection rationale: Based on results of preliminary feeding studies

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
- Cage side observations checked: changes in clinical condition and behaviour and significant changes were recorded.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: on Days 8, 15, 22, 29
- observations included, but were not limited to the assessment of autonomic function (e.g. lacrimation, salivation, piloerection, exophthalmus, urination, defecation, pupillary function, ptosis); description, incidence and severity of any convulsions, tremors, abnormal motor function, alteration in respiration, reactivity to stimuli, changes in the level of arousal, sensorimotor responses.

BODY WEIGHT: Yes, measurement in replicate order immediately before feeding and at the same day once a week until termination.

FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each animal determined and mean daily diet consumption calculated as mg food/kg body weight: Yes, on a weekly basis
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes.

HAEMATOLOGY: Yes
At termination, all rats were bled by cardiac puncture and samples were collected. Parameters determined: Hemoglobin, red cell count, haematocrit, mean cell volume, mean cell haemoglobin, mean cell haemoglobin concentration, platelet count, white blood cell count, neutrophil count, lymphocyte count, monocyte count, eosinophil count, prothrombin time and kaolin-cephalin time.

CLINICAL CHEMISTRY: Yes
At termination, all rats were bled by cardiac puncture and samples were collected. Parameters determined: Albumin, total protein, cholesterol, triglycerides, urea, creatinine, glucose, total bilirubin and alkaline phosphatase, plasma gamma-glutamyl transferase, plasma alanine aminotransferase, plasma aspartate aminotransferase, plasma creatine kinase, plasma sodium, plasma potassium, plasma chloride, plasma calcium and plasma phosphorus.

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: on Days 8, 15, 22, 29
- Dose groups that were examined: All
- Battery of functions tested: sensory activity / grip strength.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes (adrenals, aorta, bladder, bone and bone marrow (femur), brain, caecum, colon, cervical lymph node, cervix, colon, duodenum, epididymis, eye and harderian gland, heart, ileum, jejunum, kidney, liver, lungs, mammary gland, mesenteric lymph node, nasal passages, esophagus, oral cavity, ovaries, pancreas, parathyroid glad, pituitary gland, prostate gland, rectum, salivary glands, sciatic nerve, seminal vesicles, skin, spinal cord, spleen, sternum, stomach, testes, thymus, thyroid gland, trachea, uterus, voluntary muscle).

Statistics:

Bodyweights were considered by analysis of covariance on initial body weight, separately for males and females. Time to tail flick and fore and hindlimb grip strength at weeks 2, 3, 4 and 5 were considered by analysis of variance, separately for both sexes. Haematological and clinical blood parameters were considered by analysis of variance. Organ weights were considered by analysis of variance and covariance on final body weight separately for both sexes.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Reduction in haemoglobin and haematocrit (males), reductions in haemoglobin, haematocrit and in white blood cell count (females).

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

Minor reductions in plasma cholesterol, triglyceride, total protein levels and plasma alanine transferase activities in males

Urinalysis findings:

not examined

Behaviour (functional findings):

no effects observed

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Increased kidney weights (males), slightly increased kidney weights (females), increased liver weights (males/females) in 5000 and 12500 ppm groups

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

kidney: increased tubular hyaline droplet formation, tubular basophilia, granular cast formation (males). liver: minimal hepatocyte hypertrophy in 4/5 male rats

Histopathological findings: neoplastic:

no effects observed

Other effects:

not examined

Details on results:

DIET ANALYSIS
All diets prepared were found to be within 4% of the target concentration. The homogeneity of the test material in the diet, determined at 1000 and 12500 ppm inclusion levels was within 2% of the overall mean concentration for both levels. Chemical stability of the test material, assessed at the 1000 and 12500 ppm inclusion levels stored at room temperature or at -20 °C was satisfactory over the period of use. Dose rates (based on nominal dietary levels) were highest at the start of the study and declined rapidly during the period of rapid growth to week 4.

MORTALITY
There were no mortalities.

FUNCTIONAL OBSERVATION BATTERY
A slightly reduced splay reflex was observed in one female of the 1000 ppm group (on days 29 and 30), in one male of the 5000 ppm group (on day 29) and in one male of the 12.500 ppm group (on day 29). As isolated observations, these were considered to be incidental. There were no differences in time to tail flick in either sex which could be attributed to treatment. The statistically significant increase in time to response observed on day 22 for males (5000 ppm) and day 8 for females (1000 ppm) were considered to be incidental to treatment in the absence of similar changes at higher dose levels. There was no evidence of any treatment related effects on forelimb or hindlimb grip strength. Any other statistically significant changes were considered spurious and unrelated to treatment with the test material.

BODY WEIGHT AND WEIGHT GAIN
There were no statistically significant effects on body weight and all final bodyweights were within 3% of the respective controls, after adjusting for initial weight differences.

FOOD CONSUMPTION
Food consumption in all treated groups remained similar to, or exceeded that, of the respective control group throughout the study.

HAEMATOLOGY
There were statistically significant reductions in haemoglobin and haematocrit at 12.500 ppm in male rats. Statistically significant reductions in haemoglobin and haematocrit were seen in females at 1000 and 5000 ppm and in white blood cell count at 1000 ppm. In the absence of a coherent dose-response relationship, these differences were considered incidental to treatment.
Any other statistically significant changes were considered spurious and unrelated to treatment with the test material.

CLINICAL CHEMISTRY
There were minor reductions in plasma cholesterol, triglyceride and total protein levels and plasma alanine transferase activities in males at 12500 ppm compared to controls. Any other statistically significant changes were considered spurious and unrelated to treatment with the test material.

ORGAN WEIGHTS
Kidney weights adjusted for body weight were statistically significantly increased in males at 5000 and 12500 ppm. All the females in the treatment groups had slightly raised kidney weights compared to control, but none achieved statistical significance, and there was no evidence of a coherent dose response relationship. Liver weights adjusted for body weight were statistically significantly increased in both sexes at 12500 ppm and in males at 5000 ppm. Any other statistically significant changes were considered spurious and unrelated to treatment with the test material.

PATHOLOGY
No treatment-related macroscopic findings were apparent at the end of the study.

HISTOPATHOLOGY
Microscopic findings: Treatment related findings were present in the kidney of male rats from all dose groups. In the 5000 and 12500 ppm dose group these comprised increased tubular hyaline droplet formation and tubular basophilia in all animals, and granular cast formation in four of the 5000 ppm animals and all of the 12500 ppm animals; the latter occurring at the cortico-medullary injection. In the 1000 ppm group, increased renal hyaline droplet formation and/or tubular basophilia were seen, but not granular cast formation. In the liver, there was minimal hepatocyte hypertrophy in 4/5 male rats in the 12500 ppm group. The increased kidney weights and microscopic findings of renal tubular basophilia, granular cast formation and increased hyaline droplet formation present in male rats at 5000 and 12.500 ppm are clearly treatment related. These findings are consistent with the well characterized light hydrocarbon nephropathy described for male rats, following to a variety of chemicals including light hydrocarbons such as unleaded gasoline and trimethyl pentane. The characteristics include an increased accumulation of hyaline droplets in male rat kidneys, the main constituent of which is alpha 2µ-globulin (Alden et al. Adv. Modern Environ Toxicol 7: 107-120 (1984); Stonard et al. Renal Heterogeneity and Target Cell Toxicity. Bach PH and Lock EA Eds, John Wiley and Sons (1985)). It is widely accepted that this phenomenon is specific to male rat and as such appears to have no relevance for man (Swenberg et al. Toxicol and App. Pharmacol. 97: 35-46 (1989)).

Key result

Dose descriptor:

NOAEL

Effect level:

1 613 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No adverse effects observed (corresponding to 12500 ppm)

Key result

Dose descriptor:

NOAEL

Effect level:

1 450 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No adverse effects observed (corresponding to 12500 ppm)

Key result

Critical effects observed:

not specified

Conclusions:

Under the study conditions, the NOAEL for repeated dose toxicity was determined to be 1450 and 1613 mg/kg/day for male and female rats, respectively.

Executive summary:

A 28 d study was conducted to determine the repeated oral dose toxicity of fatty acids, C5-10, esters with pentraerythritol according to OECD Guideline 407, in compliance with GLP. The test substance was administered at concentrations of 1000, 5000 and 12500 ppm (corresponding to 112, 562 and 1450 mg/kg bw/day for male and 119, 586 and 1613 mg/kg bw/day for female rats) to 5 Alpk:APfSD rats per sex and dose for 28 consecutive days. Control animals (5 per sex and dose) received plain diet. There were no toxicologically significant effects on body weight, food consumption and clinical condition and no mortality up to and including the highest dose level. Changes in clinical chemistry and red cell-related parameters were observed in male rats at 12500 ppm, but these were minor and considered not to be of toxicological significance. A minimal hepatocyte hypertrophy present in males of the 12500 ppm group was observed and considered to be evidence of an adaptive response. Microscopic examination of the kidneys from male animals from all dose groups revealed an increase in hyaline droplet formation (the main constituent of which is alpha-2µ-globulin) and tubular basophilia. This phenomenon is widely accepted to be specific to the male rat and as such is considered to have no relevance to man. Under the study conditions, the NOAEL for repeated dose toxicity was determined to be 1450 and 1613 mg/kg/day for male and female rats, respectively (Croda, 1993).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 450 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Good quality studies

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the absence of specific studies with the test substance, repeated dose toxicity was assessed based on data for substances representative of the main constituents, which can be categorised as pentaerythritol esters (PE) and glycerol esters (GE). The results are presented below:

 

Oral

 

Pentaerythritol esters

Study 1:

A 28 d study was conducted to determine the repeated oral dose toxicity of fatty acids, C5-10, esters with pentraerythritol according to OECD Guideline 407, in compliance with GLP. The test substance was administered at concentrations of 1000, 5000 and 12500 ppm (corresponding to 112, 562 and 1450 mg/kg bw/day for male and 119, 586 and 1613 mg/kg bw/day for female rats) to 5 Alpk:APfSD rats per sex and dose for 28 consecutive days. Control animals (5 per sex and dose) received plain diet. There were no toxicologically significant effects on body weight, food consumption and clinical condition and no mortality up to and including the highest dose level. Changes in clinical chemistry and red cell-related parameters were observed in male rats at 12500 ppm, but these were minor and considered not to be of toxicological significance. A minimal hepatocyte hypertrophy present in males of the 12500 ppm group was observed and considered to be evidence of an adaptive response. Microscopic examination of the kidneys from male animals from all dose groups revealed an increase in hyaline droplet formation (the main constituent of which is alpha-2µ-globulin) and tubular basophilia. This phenomenon is widely accepted to be specific to the male rat and as such is considered to have no relevance to man. Under the study conditions, the NOAEL for repeated dose toxicity was determined to be 1450 and 1613 mg/kg/day for male and female rats, respectively (Croda, 1993).

Glycerol esters (GE)

Study 1:

A study was conducted to determine the subchronic oral toxicity of glycerides, C16-18 and C18-unsatd. (in the form of pine nut oil) according to OECD Guideline 408, in compliance with GLP. The test substance was administered through the diet to three groups, each of ten male and ten female Wistar Crl:Wi(Han) strain rats, for up to 98 and 100 consecutive days, at dose levels of 0, 1, 5 and 15% per day. In Week 12, a functional observation test was carried out. At Week 13, ophthalmoscopic examinations were conducted. Clinical signs, bodyweight development, food intake and mortality/viability were monitored during the study. Haematology and blood chemistry were evaluated for all animals at the end of the treatment period. All animals were subjected to gross necropsy and macroscopic examination and a complete histopathological examination was performed. No toxicological significant changes were observed. Under the study conditions, the NOAEL for subchronic oral toxicity was determined to be 8866 and 10242 mg/kg bw/day for male and female rats, respectively (Gerrit, 2009).

Dermal

 

A repeated dose dermal toxicity study is not required because OECD 407 and 98 d oral studies are available with the read across substances of the constituents. Further, given the physico-chemical properties of the substance, dermal absorption is not expected to be higher than via the oral route. Hence, testing via dermal route will less likely result in any additional hazard identification and further testing involving vertebrate animals may be omitted, in accordance with Annex XI (1.2) of the REACH regulation. Nevertheless, the risk assessment for this route has been carried out based on oral studies available with the read across substances, using appropriate route-to-route extrapolation assessment factors as per the ECHA Guidance R.8.

 

Inhalation

 

The substance is a viscous liquid with a low vapour pressure at room temperature. Due to its physical state and physical chemical properties it is unlikely that this substance will form inhalable dust, mist or fumes during normal processing and use conditions. In case inhalable forms of the substance are created under particular conditions (e. g. spraying, elevated temperature/pressure), appropriate risk management measures such as closed systems, exhaust ventilation or wearing of respirators are implemented to control exposure. Under such conditions, the risk to humans following inhalation exposure can be considered minimal and further testing involving vertebrate animals may be omitted, in accordance with Annex XI (1.2) of the REACH regulation. Nevertheless, the risk assessment for this route has been carried out based on oral studies available with the read across substances, using appropriate route-to-route extrapolation assessment factors as per the ECHA Guidance R.8.

Justification for classification or non-classification

Based on the information available for its main constituents, the test substance is not considered to meet the requirements for STOT RE classification according to the EU CLP (Regulation 1272/2008/EC) criteria.