7-methyl-3-methyleneocta-1,6-diene

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1993

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Study protocol is different from the standard OECD guidelines with ; absence of individual and historical control data, making the interpretation of results difficult.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Materials and methods

Principles of method if other than guideline:

Method: β-Myrcene (0, 250, 500, 1000 or 1500 mg/kg bw/day) in corn oil was given orally to female Wistar rats from Day 15 of pregnancy to postnatal Day 21 and peri- and postnatal developmental toxicity effects were evaluated.

GLP compliance:

not specified

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

7-methyl-3-methyleneocta-1,6-diene

EC Number:

204-622-5

EC Name:

7-methyl-3-methyleneocta-1,6-diene

Cas Number:

123-35-3

Molecular formula:

C10H16

IUPAC Name:

7-methyl-3-methylideneocta-1,6-diene

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Day 15 of pregnancy to postnatal Day 21

Frequency of treatment:

Once daily

Duration of test:

Day 15 of pregnancy of F0 generation to postnatal Day 4 of F2 generation

Doses / concentrations

Remarks:

Doses / Concentrations:
250, 500, 1000 or 1500 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

20, 12, 18, 14 and 15 pregnant females at concentrations of 0, 250, 500, 1000 and 1500 mg/kg bw/day, respectively

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

Key result

Dose descriptor:

NOAEL

Remarks:

for peri- and postnatal developmental toxicity

Effect level:

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

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Decreased birth weight, increased perinatal mortality and delayed day of appearance of landmarks of postnatal development (at doses ≥ 500 mg/kg bw/day); impaired fertility in female offspring (at 1000 and 1500 mg/kg bw/day)

Observed effects

PERINATAL EFFECTS:
- Mortality: 5/15 rats died in 1500 mg/kg bw/day group; no mortality at other dose levels
- Body weight: Statistically significant decrease in body weight was observed at 1000 mg/kg bw/day (on gestation Day 20) and 1500 mg/kg bw/day (on gestation Day 20 and postnatal Day 1).
- Duration of pregnancy: Not affected at any dose levels; labour duration higher (> 6 hour) at 500 mg/kg bw/day (1 dam) and 1000 mg/kg bw/day (3 dams)
- Litter size: No treatment-related effects were observed but a higher proportion of stillbirths were detected in 1000 mg/kg bw/day group
- Newborn weight: Statistically significant lower newborn weight at doses ≥ 500 mg/kg bw/day (6.1 ± 0.35, 5.5 ± 0.74, 5.2 ± 0.94 and 4.9 ± 0.90 g at 0, 500, 1000 and 1500 mg/kg bw/day, respectively)

POSTNATAL EFFECTS
- Postnatal mortality: Statistically significant increase was observed at 500, 1000 and 1500 mg/kg bw/day during lactation period (1.8, 1.7, 14.4, 24.4 and 16.8% at 0, 250, 500, 1000 and 1500 mg/kg bw/day, respectively)
- Postnatal development: Day of first detection of primary coat was delayed with 500 mg/kg bw/day and higher doses, and the days of ear unfolding and eye opening were delayed with 1000 and 1500 mg/kg bw/day
- Fertility: Statistically significant effect was observed on the fertility of the offspring at 500, 1000 or 1500 mg/kg bw/day. Subsequent examination on male rats suggested that the reproductive failures were probably attributable to female infertility.

Any other information on results incl. tables

Table 1. Maternal weight changes (g)

 

Myrcene (mg/kg bw/day)	Days
	Day 0 of pregnancy	Day 20 of pregnancy	Postnatal Day 1
0	210.9 ± 13.5	314.4 ± 19.2	240.1 ± 15.7
250	208.8 ± 8.9	307.3 ± 22.6	239.1 ± 18.7
500	205.2 ± 13.4	306.1 ± 26.7	231.5 ± 23.1
1000	207.4 ± 18.8	293.0 ± 27.5*	228.5 ± 22.4
1500	209.8 ± 12.3	288.4 ± 29.4*	223.8 ± 17.9*

 

Table 2: Physical signs of postnatal development of offspring

 

Myrcene (mg/kg bw/day)	Parameters
	Ear unfolding (%) on postnatal Day 4	Primary coat (%) on postnatal Day 6	Eye opening (%) on postnatal Day 15
0	98	90	39.4
250	97.5	100	47
500	95.8	62.4*	38.7
1000	76.5*	39.2*	19.8*
1500	88.5*	61.2*	20*

 

Table 3: Outcome of fertility tests

 

Myrcene (mg/kg bw/day)	Outcome
	1st mating; no. mated/no. giving birth (%)	1st + 2nd mating; no. mated/no. giving birth (%)
0	54/50 (92.6)	54/53 (98.2)
250	31/31 (100)	31/31 (100)
500	43/34 (79.1)*	43/42 (97.7)
1000	24/16 (66.7)*	24/19 (79.2)*
1500	26/19 (73.1)*	26/20 (76.9)*

*significantly different (P < 0.05) from controls.

Applicant's summary and conclusion

Conclusions:

The no-observed-adverse-effect level (NOAEL) for peri- and postnatal developmental toxicity of β-myrcene administered orally (gavage) was considered to be 250 mg/kg bw/day in Wistar rats.

Executive summary:

A study was conducted to evaluate the peri- and postnatal developmental toxicity of β-myrcene in the Wistar rats.

 

β -Myrcene (0, 250, 500, 1000 and 1500 mg/kg bw/day) in corn oil was given orally to female Wistar rats from Day 15 of pregnancy to postnatal Day 21. The progeny was examined at birth and subsequently to weaning. Mortality, weight gain and physical signs of postnatal development (ear unfolding, incisor eruption, fur development and eye opening) were evaluated. When the exposed offspring reached maturity (120 days) their reproductive capacity was assessed.

 

No adverse effects on the offspring were seen with the lowest dose tested, but at 500 mg/kg bw/day and higher doses, decreased birth weight, increased perinatal mortality and delayed day of appearance of landmarks of postnatal development were observed. Moreover, fertility was impaired in female offspring exposed to the two highest doses of β-myrcene.

 

Therefore, the no-observed-adverse-effect level (NOAEL) for peri- and postnatal developmental toxicity of β-myrcene administered orally (gavage) was considered to be 250 mg/kg bw/day in Wistar rats.