Fatty acids, C10-20-neo, potassium salts

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.67 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC Technical Report No. 110

Overall assessment factor (AF):

18

Modified dose descriptor starting point:

NOAEC

Value:

66.12 mg/m³

Explanation for the modification of the dose descriptor starting point:

Convert oral NOAEL to Inhalation NOAEC: 75 mg/kg/day x [1/0.38 x rat oral absorption (50%) / human inhalation absorption (100%) x (6.7/10)] = 66.12 mg/m3

AF for dose response relationship:

1

Justification:

Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.

AF for differences in duration of exposure:

6

Justification:

Extrapolation from subacute study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment and in ECETOC Technical Report 110.

AF for interspecies differences (allometric scaling):

1

Justification:

Differences in species addressed in calculation of dose descriptor starting point.

AF for other interspecies differences:

1

Justification:

All interspecies differences accounted for by allometric scaling. Default value in ECETOC Technical Report No. 110.

AF for intraspecies differences:

3

Justification:

Default value in ECETOC Technical Report No. 110.

AF for the quality of the whole database:

1

Justification:

Information taken from one 2 year chronic study on KCl and one 422 study on crude tall oil. Both were K1 studies that were only given K2 values due to read across.

AF for remaining uncertainties:

1

Justification:

Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment and ECETOC Guidance No. 110.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.04 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC Guidance No. 110

Overall assessment factor (AF):

72

Modified dose descriptor starting point:

NOAEL

Value:

75 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Assumed dermal absorption is equal to oral absorption as a precautionary measure.

AF for dose response relationship:

1

Justification:

Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.

AF for differences in duration of exposure:

6

Justification:

Extrapolation from subacute study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment and ECETOC Guidance No. 110.

AF for interspecies differences (allometric scaling):

4

Justification:

Default value in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment and ECETOC Guidance No. 110.

AF for other interspecies differences:

1

Justification:

All species differences accounted for in allometric scaling according to ECETOC Guidance 110.

AF for intraspecies differences:

3

Justification:

Default value in ECETOC Technical Report No. 110.

AF for the quality of the whole database:

1

Justification:

Information taken from one 2 year chronic study on KCl and one 422 study on crude tall oil. Both were K1 studies that were only given K2 values due to read across.

AF for remaining uncertainties:

1

Justification:

Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment and ECETOC Guidance No. 110.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

Data are available both on the test substance itself as well as on several substances which are suitable for read across. Based on these data, the substance is classified as an eye irritant and a Category 2 developmental hazard. The NOAEL of 75 mg/kg bw/day is based on a 422 study on the test substance. The effects seen at 250 mg/kg bw/day only included slight centrilobular hypertrophy of hepatocytes in female and an increase in liver weights in both sexes. These effects were not considered significant or severe, so there is no requirement for a specific target organ toxicity classification. No reproductive toxicity was seen in any dose group. There was an increase in pup mortality at 250 and 750 mg/kg bw/day, which led to a decreased litter size. As this could not be excluded as a test item related effect, the substance is classified as a developmental hazard, category 2.

The test substance was not toxic by acute oral administration. Naphthenic acid and potassium nitrate were non-toxic by acute dermal administration. While dermal absorption is unlikely, dermal absorption was considered equal to oral absorption in the DNEL calculations as a precautionary measure.

The substance did not show evidence of skin sensitization or skin irritation, but it is considered an eye irritant. However, DNELs for long term systemic effects are considered sufficient to protect from local and acute effects. Therefore, local effect and acute effect DNELs were not generated.

Finally, neither naphthenic acid nor potassium salts are considered genotoxic based on multiple in-vitro assays. A mouse lymphoma assay on the test substance was also negative.

All assessment factors were the default values taken from ECETOC Technical Report No. 110, Guidance on Assessment Factors to Derive a DNEL. To prepare this publication, ECETOC conducted an extensive and documented review of the scientific literature. Therefore, the AF supplied in the ECETOC document are considered valid and scientifically justifiable.

Repeated Dose - 422 - Summary

A combined repeated dose toxicity study with reproduction/developmental toxicity screening test was carried out in order to assess the test material in accordance with the standardised guidelines OECD 422 and EPA OPPTS 870.3650 under GLP conditions.

Four groups of ten male and ten female Wistar Han rats were exposed by oral gavage to the test material at 0, 75, 250 and 750 mg/kg/day in propylene glycol. Males were exposed for 28 days (2 weeks prior to mating, during mating, and up to termination) and females were exposed for 41 to 55 days (2 weeks prior to mating, during mating, during postcoitum and during at least 4 days of lactation).

Animals were evaluated for mortality/viability, clinical signs, functional observations and locomotor activity, body weight and food consumption, clinical pathology, macroscopy at termination, organ weights and histopathology on a selection of tissues and reproduction/developmental parameters.

Changes in clinical biochemistry parameters, increased organ weights, macroscopically enlarged livers and microscopic findings in the liver (centrilobular hepatocytic hypertrophy) and thyroids (follicular hyperplasia and hypertrophy) characterised parental toxicity at 750 mg/kg. Higher liver weights and liver to body weight ratios were seen for both sexes and a slight degree of centrilobular hypertrophy of the liver was also seen for females at 250 mg/kg.

No toxicologically relevant changes were noted in any of the remaining parental parameters.

Under the conditions of this study, the NOAEL was determined to be 75 mg/kg bw/day for repeated dose toxicity. As no significant or severe effects were seen at the 250 mg/kg bw/day dose group, no classification for specific target organ toxicity due to repeat exposure (STOT RE) is necessary in accordance with EU criteria.

 

The mean litter size was smaller at 750 mg/kg than controls and higher pup mortality was evident at both 250 and 750 mg/kg. No toxicologically significant changes were noted in any of the remaining developmental parameters investigated in this study (i.e. gestation index and duration, parturition, maternal care and clinical signs, bodyweights and macroscopy of pups).

Under the conditions of this study, the NOAEL for developmental parameters is considered to be 75 mg/kg/day. The test material therefore requires classification in accordance with EU criteria for developmental toxicity as Category 2.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

Exposure to the general population is not expected based on the substance use pattern. Fatty acids, C10-20-neo, potassium salts (iso-naphthenic acids, potassium salts) is intended for use within industrial and professional use sectors only, and no uses by the general population are anticipated. As such it is considered justified not to derive a DNEL for this type of exposure.