Lauric acid, monoester with propane-1,2-diol

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
A read-across approach has been suggested based on the metabolism of the common structure of propylene glycol fatty acid esters. Read-across is implemented from already existing data from testing on Dapro FX511, on metabolism products (fatty acid and propylene glycol) and on propylene glycol monolaurate.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical:

Dapro FX 511
EC Number: 285-503-5
CAS Number: 85114-00-7

Target chemical:

RM1004755:
Einecs No. 248-315-4
CAS No. 27194-74-7

See read-across justification report in section 13


3. ANALOGUE APPROACH JUSTIFICATION
A matrix of data has been created using the Dapro FX511 REACH dossier, read-across document for aquatic tox from Dapro FX510 (source) to Dapro FX511 (target), a HPV test plan for the glycol esters of the aliphatic esters chemicals (including Propylene glycol, monostearate (CAS 1323-39-3)) and a Petition to include propylene glycol monolaurate into 7 CFR 205 (constituent of RM1004755).
See read-across justification report in section 13


4. DATA MATRIX

Data matrix is given in read-across justification report in section 13

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

RD 15134

IUPAC Name:

RD 15134

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): RD 15134
- Physical state: Liquid
- Analytical purity: 95.8%
- Lot/batch No.: 85114-00-7
- Expiration date of the lot/batch: 01-June-2018
- Storage condition of test material: room temperature
- Other:

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

90 days

Frequency of treatment:

Once daily at approximately the same time each day

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 250, 500, 1000 mg/kg/day
Basis:
actual ingested

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

250 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

histopathology: non-neoplastic

2

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No test substance effects seen at 1000 mg/kg bw/day the highest dose level tested

Remarks on result:

not determinable due to adverse toxic effects at highest dose / concentration tested

Target system / organ toxicity

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

500 mg/kg bw/day (actual dose received)

System:

urinary

Organ:

kidney

Treatment related:

yes

Dose response relationship:

not specified

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

t is concluded that oral administration of RD 15134, a coalescing agent, to Sprague-Dawley Crl:CD(SD) rats at 250, 500 or 1000 mg/kg/day for 13 weeks was relatively well-tolerated at doses in males at 250 mg/kg/day and in females up to 1000 mg/kg/day. In males, a dose of 500 mg/kg/day or above resulted in hyaline droplets and tubular basophilia with interstitial fibrosis in the kidney, with an associated increase in kidney weight and urea concentration.
It is therefore considered that the no-observed-adverse- effect-level (NOAEL) was 250 mg/kg/day in males, based primarily on the changes seen in the kidneys, and 1000 mg/kg/day in females.