1,2,3-Propanetriol, mono- and diformates

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: 13-week study

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP guideline study, according to and exceeding the requirements of the OECD TG 413 with additional emphasis on some of the male and female reproductive parameters. Tested with the source substance formic acid (CAS No. 64-18-6). For details on read-across refer to the attached read-across report.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1992

Reference 2

Reference Type:

secondary source

Title:

Unnamed

Year:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 413

Deviations:

yes

Remarks:

emphasis on some of the male and female reproductive parameters including sperm morphology and vaginal cytology

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Formic acid

EC Number:

200-579-1

EC Name:

Formic acid

Cas Number:

64-18-6

IUPAC Name:

formic acid

Test material form:

not specified

Details on test material:

95 % formic acid / 5 % water

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Exposure period: 13 weeks

Frequency of treatment:

5 days/week, 6 h/day

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0; 8; 16; 32; 64; 128 ppm (as vapour)
Basis:

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0; 0.015; 0.031; 0.120; 0.241 mg/m3
Basis:

No. of animals per sex per dose:

10/sex/group

Control animals:

yes

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes

Oestrous cyclicity (parental animals):

oestrus cyclicity analysed in rats of the 0, 8, 32, 128 ppm groups

Sperm parameters (parental animals):

sperm motility and concentration were analysed in rats of the 0, 8, 32, 128 ppm groups

Postmortem examinations (offspring):

At sacrifice, among other organs, the right testis was weighed

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

not specified

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

not specified

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

not examined

Details on results (P0)

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS): body weight gains of the male rats of the 8, 16, 32 and 64 ppm groups
were slightly increased as compared to the control rats

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS): no effects observed

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS): no effects were observed on testicular weight, epididymal weight, sperm motility and epididymal and testicular sperm concentration

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

0.244 mg/L air

Results: F1 generation

General toxicity (F1)

Clinical signs:

not examined

Mortality / viability:

not examined

Body weight and weight changes:

not examined

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

Result: no effects on sperm motility, density, and testes and epididymal weight,  or estrous cycle length
RS-Freetext:
Male and female reproductive organs: 
Regarding the male and female reproductive organs, there
were no effects on sperm motility, density or testicular or
epididymal weights, and no changes were seen in the length
of the estrous cycle at any dose.

===========================================================
Parameter          Exposure concentration (ppm)   
                    0         8         32          128
-----------------------------------------------------------
Males
Weight (g)
right testis      1.40      1.45       1.47       1.41
left epididymis   0.449     0.461      0.469      0.460   
left epididymal   0.167     0.171      0.174      0.169
tail

Spermatozoal measurements
Motility (%)     91+/-1     91+/-1     91+/-1     88+/-1
Concentration   658+/-21   706+/-21   580+/-60   651+/-29  
(10E06/g)


Females
Estrous cycle    4.80       4.75       4.95        4.95
length (d)       
===========================================================

The NOAEC was therefore 0.244 mg/l for systemic toxicity and
effects ob reproductive organs, and 0.122 mg/l for local
irritation in the respiratory tract.

Applicant's summary and conclusion

Conclusions:

Formic acid does not have adverse effects on F344 male and female rats when exposed via inhalation to concentrations up to 128 ppm.

Executive summary:

In a reproduction study, formic acid was administered to 10 F344 rats/sex/dose via inhalation at dose levels of 0, 8, 16, 32, 64, and 128 ppm (0, 15, 30, 120, or 240 mg/kg bw/day).  

No effects were observed on oestrus cyclicity, testicular weight, epididymal weight, sperm motility and epididymal and testicular sperm concentration. Body weight gains of the male rats of the 8, 16, 32 and 64 ppm groups were slightly increased as compared to the control rats. The NOAEL is 0.244 mg/L air in males and females.  

This study is acceptable and satisfies the guideline requirement for a 90-daysubchronic inhalation toxicity test to examine reproductive endpoints; OECD 413, in rodents.