LINEAR ALKYLBENZENE SULFONATE (LAS) - UNEP Chemicals

OECD SIDS LINEAR ALKYLBENZENE SULFONATE (LAS)
3.1.9 Developmental Toxicity
A substantial number of studies have been conducted to determine the developmental toxicity and
teratogenicity characteristics of LAS. These studies have included exposures to several species
(rats, rabbits, mice) by the oral route via gavage, in the diet, or in the drinking water, and by the
dermal exposure route. Table 7 summarizes the maternal and fetal data from the available
developmental studies.
Oral exposure
In one representative oral exposure study, LAS at a dose of 0.1% was administered to 40 female
rats and 22 female rabbits in drinking water from day 6 to 15 (rats) and day 6 to 18 (rabbits) of
pregnancy (Endo et al. 1980; European Commission 2000). This dose corresponds to 70 and 250
mg/kg bw/day for rats and rabbits, respectively. The only effect on the dams was a slight inhibition
of body weight gain in the rabbits. No significant effects were observed in the litter parameters of
both species as compared to the controls. Delayed ossification was observed in rabbits, but there
was no increase in malformations in either the rabbits or the rats. Consequently, the fetal LOAEL
for the rabbit is 250 mg/kg bw/day, which is also the maternal LOAEL. The NOAELs (maternal
and fetal) for the rat are 70 mg/kg bw/day.
Maternal effects in other oral exposure studies ranged from no effects to severe toxicity and death in
some studies. Common effects included decreased body weights, gastrointestinal effects, and
diarrhea. Some studies resulted in anorexia. In two oral feed studies, no maternal effects were
observed (Nolen et al., 1975; Tiba et al., 1976). However, in four gavage studies, deaths occurred at
higher doses tested. Specifically, 1 CD rat died at 600 mg/kg bw/day, although this effect was not
conclusively related to treatment (Palmer et al., 1975a). In a study with Charles-River pathogen-free
mice of the CD-1 strain, 35% of the animals died at 300 mg/kg bw/day and 90% died at 600 mg/kg
bw/day (Palmer and Lovell, 1971b). A study in New Zealand white rabbits also resulted in severe
maternal toxicity and 85 and 100% deaths at 300 and 600 mg/kg bw/day, respectively (Palmer and
Neuff, 1971; Palmer et al., 1975a). Finally, in a study in ICR mice, two animals died at 300 mg/kg
bw/day (Shiobara and Imahori, 1976). In studies where maternal toxicity was observed, LOAELs
ranged from 100-400 mg/kg bw/day, similar to the results of repeated-dose toxicity studies (section
3.1.5) where LOAELs from oral exposures ranged from 115-750 mg/kg bw/day.
In nine other oral exposure studies the results on offspring were similar to those of Endo et al. (1980)
reported above, with litter effects, where observed, only occurring at maternally toxic doses (Palmer
and Lovell 1971a; Palmer et al. 1975a; Nolen et al. 1975; Tiba et al., 1976; Palmer and Lovell 1971b;
Takahashi et al. 1975; Shiobara and Imahori 1976; Palmer and Neuff 1971). In a drinking water
study in rats, a dose of 600 mg/kg bw/day that produced maternal toxicity resulted in marginal
retardation of sternebral ossification in offspring (Palmer and Lovell, 1971a). In another study in
which maternal toxicity was observed, effects in mice and rabbit offspring included increased fetal
loss (at 300 and 600 mg/kg bw/day), and reduced litter size and minor skeletal or visceral anomalies
(mice at 300 mg/kg bw/day) (Palmer et al., 1975a). In a third study (mice, gavage) in which maternal
toxicity was observed, there was delayed ossification among living fetuses and decreased body
weights at the highest dose tested (300 mg/kg bw/day) but no increase in malformations (Shiobara
and Imahori, 1976). In three other studies with maternal toxicity, no offspring effects were observed
at the highest doses tested, 600 mg/kg bw/day in a gavage study in rats (Palmer et al., 1975a), 600
mg/kg bw/day in drinking water study in mice (Palmer and Lovell, 1971b) or 400 mg/kg bw/day in a
gavage study in mice (Takahashi et al. 1975). Three other oral studies reported no maternal or
offspring effects at the highest doses tested, 225 mg/kg bw/day in a rat feeding study (Nolen et al.
1975), 780 mg/kg bw/day in a second rat feeding study (Tiba et al. 1976) or 135 mg/kg bw/day in a
rabbit feeding study (Nolen et al. 1975).
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