Lithium dodecyl sulphate

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was well conducted and scientifically acceptable for assessment . However, available data are summarised and therefore not detailed.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

The effects of prolonged subtoxic lithium ingestion on pregnancy in rats

Author:

Trautner, E.M.

Bibliographic source:

Austral J Exp Biol. 1958;36:305-22

Report date:

1958

Materials and methods

Principles of method if other than guideline:

No common testing procedure was followed. The publication comprised of a variety of tests. For details please refer to "Any other information on results"

GLP compliance:

no

Remarks:

study performed prior to GLP

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Lithium chloride

EC Number:

231-212-3

EC Name:

Lithium chloride

Cas Number:

7447-41-8

IUPAC Name:

lithium chloride

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
20 mmol/L
Basis:
nominal in water

Doses / concentrations 2

Remarks:

Doses / Concentrations:
2 mmol/kg bw/d
Basis:
actual ingested

Doses / concentrations 3

Remarks:

Doses / Concentrations:
13.9 mg Li /kg bw/d
Basis:
actual ingested

Control animals:

yes, concurrent vehicle

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

Trautner (1958) reported a number of developmental/reproductive experiments in Wistar rats.

In the first experiment animals were treated with lithium in drinking water at 20 mmol/L for 3-7 weeks prior to mating and during gestation. No signs of toxicity or behavioral changes were observed. The mean time until pregnancy occurred, was 6 days for control and treated groups. 90 of 100 control females (90%) and 46 of 52 treated females (88%) gave birth to offspring. No damage to mothers or litters were noted.

In another experiment, 6 animals per sex and group received lithium in drinking water at 25 mmol/L beginning 17 days before mating. Treatment of females was continued during gestation. Under this experimental setting the rate of pregnant females was decreased when females were treated with lithium. In case only males were treated no effect on the pregnancy rate was observed. The authors stated that the females remained “healthy” through pregnancy. However, no data on maternal toxicity were reported. At 30 mmol/L already death occurred in the repeated dose study of Trautner (1958). No effects were observed when only the males were treated. Therefore, this effect might be due to maternal toxicity.

In the 3rd experiment, male and female rats were treated with lithium in drinking water at 20 mmol/L for presumably 17 days (not specified). No data on maternal or systemic toxicity were reported. 14/15 and 16/17 females gave birth when only males or females were treated with lithium, respectively. When both sexes received lithium 5/7 females delivered offspring. No effect on frequency of pregnancy was reported, although frequency in the latter group might be lower.

In experiment 4, rats received lithium chloride at 20 mmol/L in water for 3-7 weeks before mating and during gestation. Animals were allowed to give birth to offspring normally. No data on maternal or systemic toxicity were available.The experiment was performed in two series. In series 1, no differences in the mean litter size between control and treated females was observed (6.1 vs. 5.9). The mean litter size of treated females in series 2 was lower when compared to control (8.7 vs. 5.7). No malformations or difference in birth weight were found in any of the pups.The early postnatal growth of treated pups was transiently retarded. No differences were observed at later stages.

In another experiment (experiment 5), female rats received lithium chloride at 20 mmol/L in water for 3-7 weeks before mating and during gestation. Animals were laparotomized on gestation day 16-18. Numbers of corpora lutea, implants, and viable fetuses were assessed. Subsequently animals were allowed to give birth to offspring. No data on maternal toxicity were given. Statistically significant reduced corpora lutea (approximately 15%), implants, and viable fetuses were observed. No malformations were observed.

The last experiment, was performed as experiment 5. However, after weaning, born pups were treated with 20 mmol/L via drinking water for a period of 6-7 months. Thereafter, female offspring was mated with untreated males and laparotomized on gestation day 16-18. No controls were used within this experiment. However, data received were compared to the animals of experiment experiment 5.

No effects on the pubs were observed and it is stated that they were “in all aspects indistinguishable from normal rats”. However upon laparotomy significantly reduced numbers of corpora lutea and viable fetuses were observed. The lower number of implantations were not statistically significant when compared to controls of experiment 5.

Taken together, no effects on the pregnancy rates and litters were observed within the first three experiments at doses being not maternal toxic. However, within experiments 4 to 6 decreased numbers of corpora lutea and also decreased numbers of implantations and thus viable fetuses were observed. Upon birth a transient delay in development was reported occasionally but overall all pups developed normal. Based on these findings lithium showed no adverse effects on development of pups but may affect the early follicle development.