Coconut oil, reaction products with boric acid (H3BO3), diethanolamine and glycerol

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on generations indicated in Effect levels (migrated information)

Type of information:

other: read across from breakdown products

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Scientific justification for addressing the endpoint using data from analogous substances and hydrolysis products

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

A review of available data on structural analogues of the registered substance, the results of which are weight of evidence to draw conclusions on the reproductive toxicity potential of the registered substance.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glycerol

EC Number:

200-289-5

EC Name:

Glycerol

Cas Number:

56-81-5

Molecular formula:

C3H8O3

IUPAC Name:

glycerol

Constituent 2

Reference substance name:

Amides, coco, N,N-bis(hydroxyethyl)

EC Number:

271-657-0

EC Name:

Amides, coco, N,N-bis(hydroxyethyl)

Cas Number:

68603-42-9

IUPAC Name:

68603-42-9

Constituent 3

Reference substance name:

Boric acid

EC Number:

233-139-2

EC Name:

Boric acid

Cas Number:

10043-35-3

Molecular formula:

H3BO3

IUPAC Name:

Boric acid

Constituent 4

Reference substance name:

9-Octadecenoic acid (Z)-, monoester with 1,2,3-propanetriol ester with boric acid (H3BO3)

EC Number:

264-092-6

EC Name:

9-Octadecenoic acid (Z)-, monoester with 1,2,3-propanetriol ester with boric acid (H3BO3)

Cas Number:

63310-16-7

Molecular formula:

UVCB - No specific molecular formula

IUPAC Name:

9-Octadecenoic acid (Z)-, monoester with 1,2,3-propanetriol ester with boric acid (H3BO3)

Test material form:

not specified

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

1

Dose descriptor:

NOEL

Effect level:

ca. 1 other: ml/kg

Based on:

test mat.

Remarks:

CAS RN 63310-16-7

Sex:

male/female

Basis for effect level:

other: Highest dose tested

2

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Remarks:

CAS RN 68603-42-9

Sex:

female

Basis for effect level:

reproductive performance

Results: F1 generation

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Remarks:

CAS RN 68603-42-9

Sex:

male/female

Basis for effect level:

other: developmental toxicity

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

REFERENCES

 

Duke, C.E., Cisson, C.M., and Wong, Z.A. 1982. Twenty-eight Day Repeated Dermal Study of [redacted] in Adult Male and Female Rats. Internal Chevron Environmental Health Center. Report No. SOCAL 1873.

 

Draize, JH and Kelley, EA. 1959. The urinary excretion of boric acid preparations following oral administration and topical applications to intact and damaged skin of rabbits.Toxicol Appl Pharmacol1:267-276.

 

ECHA Transitional Annex XV Dossier on Boric Acid. 2010

 

Environmental Protection Agency (EPA) Fatty Nitrogen Derived Amides High Production Volume (HPV) Chemicals Challenge. 2001

 

Loeser, A., Bornmann, C., Crosskinsky, L., Hess, G., Kopf, R., Ritter,K.,Schmitz, A., Stuermer, E., and Wegener, H.(1954).Diethylene glycol. Pharmacology and toxicology of polyglycols. Naunyn-SchmiedebergsArch.Expt. Pathol. Pharmakol.221, 14-33.In:Informatics,Ref.69.

 

National Toxicology Program (NTP). 2001. “Diethanolamine Condensate (CAS No. 68603-42-9) in F344/N Rats and B6C3F1 Mice (Dermal Studies)”. NTP TR 479/NIH. Publication No. 01-3969.

 

NTIS US Department of Commerce. 1974. Teratological evaluation of glycerine in mice, rats and rabbits. Report No. PB-234876.

 

Wegener, H. 1953. Über die Fortpflanzungsfähigkeit der Ratte nach Einwirkung von Diäthylenglykol. Arch exper Path u Pharmakol,220:414-417

 

Weir, RJ and Fisher, RS. 1972. Toxicologic studies on borax and boric acid. Toxicol Appl Pharmacol. 23: 351-364.

 

Applicant's summary and conclusion

Conclusions:

Read-across to support the registration of CAS RN 1428353-74-5 using hydrolytic and metabolic breakdown products is considered to be acceptable. None of the data on the hydrolytic and metabolic breakdown products showed these substances to be toxic to reproduction and therefore the registered substance is also considered not to be toxic to reproduction.

Executive summary:

To date, there is no existing reproductive and developmental toxicology data on the registered substance (CASRN 1428353-74-5); however, reproductive and developmental toxicity data exist for glycerol (CASRN 56-81-5), amines, coco, N, N-bis (hydroxyethyl) (CASRN 68603-42-9), and for boric acid (CASRN 10043 -35-3), breakdown products of the substance to be registered. Additionally, a repeated dose dermal study conducted on borated glycerol monooleate (CASRN 63310-16-7) demonstrates no toxicological effects to male and female reproductive organs (Table 1.) The read across reproductive and developmental data presented below demonstrates that the substance to be registered is not expected to be a reproductive and/or a developmental toxicant.

 

A two-generation fertility study conducted on rats demonstrated that glycerin (CASRN 56-81-5), administered via oral gavage, had no effect on growth, fertility, or reproductive performance (Wegener, 1953). Administration of 1.0 ml/kg (50% aqueous glycerol solution) to rats had no adverse effects on development, survival, internal organs, skeletal system, or hepatic glycogen (Loeser et al., 1954). Likewise, another developmental toxicity set of studies conducted on mice, rats, and rabbits demonstrated no effect on developmental toxicity of offspring of female animals dosed with glycerin (NTIS, 1974). These studies clearly highlight that glycerin is not a reproductive or a developmental toxicant.

 

A developmental study (similar to OECD 414) conducted (oral exposure) on CASRN 68603-42-9 resulted in maternal and developmental NOAELs greater than the highest dose tested, 1000 mg/kg/day. The only recorded treatment related effects were salivation and propulsion of the head during dose administration. This study validates that this substance is not expected to be a reproductive or a developmental toxicant.

 

Animal studies investigating the reproductive toxicity of boric acid have resulted in decreased sperm viability and testicular atrophy in males and decreased ovulation in females. These effects occurred at very high doses that exceed human exposure levels. Epidemiological studies have not discovered adverse reproductive effects in even the highest exposed group- workers who mine and refine borates. These human studies are considered inconclusive due in part to the low sample size and have been considered insufficient by ECHA for the hazard evaluation of boric acid. The substance to be registered does not contain detectable levels of residual boric acid and will not hydrolyze to boric acid under normal use conditions to the worker or consumer. In the worst case scenario, the dermal absorption of boric acid in humans is relatively low at <0.3% (Draize and Kelley, 1959) and would not pose a risk for reproductive or developmental toxicity via dermal route. A repeated dose dermal study conducted on a similar borated material (CASRN 91052-28-7) via dermal route demonstrated a NOEL greater than 1ml/kg (neat). Changes to reproductive organs were not considered biologically significant due to the absence of other histopathological changes.

Additionally, a repeated dose dermal toxicity study demonstrated no toxicological effects on male and female reproductive organs resulted from administration of 5.0 g/kg of undiluted CASRN63310-16-7 to abraded skin. Study results indicated no deaths or signs of toxicity in all five rabbits of each sex during the study. Additionally, no gross pathological changes were shown to be attributed to administered test material at necropsy. 

 

Collectively,these studies demonstrate that substance to be registered does not meet the criteria to be classified as a reproductive toxicant according to CLP.