Two-Generation Reproductive Toxicity Study of Resorcinol Administered Via Drinking Water to Crl:CD(SD) Rats

Abstract

The potential adverse effects of resorcinol, delivered via drinking water at 0, 120, 360, 1000, and 3000 mg/L (palatability limit), were assessed in a regulatory guideline compliant two-generation reproduction study in Crl:CD(SD) rats. Expanded end points of thyroid gland (TG) function were added because of clinical case reports indicating human TG toxicity. Average daily resorcinol intake (mg/kg) at the 3000 mg/L concentration was 233 in F0 and F1 males, whereas in females it was 304 (premating/gestation) and 660 (lactation). No resorcinol ingestion-related clinical signs of toxicity were observed. Furthermore, neither gross morphologic anomalies nor effects on reproductive function or thyroid hormone levels were detectable. Body weight reductions occurred in 3000 mg/L F0 and F1 animals and were more pronounced in males. However, there was no evidence of either cumulative toxicity in the second generation or of enhanced sensitivity to resorcinol in pregnant/lactating females. Water intake was lower in 3000 mg/L rats of both generations and intermittently, to a lesser extent, at 1000 mg/L; however, concurrent feed intake and utilization were unaffected. Decreased TG follicular colloid content (conventional histopathology; confirmed by quantitative stereomicroscopy) in the 3000 mg/L F0 males was attributed to resorcinol but not considered adverse. The 3000 mg/L intake level appeared to have caused an adaptive thyroid response to a new homeostatic level with no adverse physiological consequences in either males (the more susceptible gender) or females. There were no differences in TG histology in F0 rats of either sex at 1000 mg/L. Thus, resorcinol intake at maximum palatability via a route and mode relevant to potential human exposures via contaminated drinking water at presently unknown environmental concentrations caused no detectable adverse effects on any reproduction or TG end points. The 3000 mg/L resorcinol exposure level was the no-observed-adverse-effect level (NOAEL) for parental systemic and offspring toxicity, while 1000 mg/L was the no-observed-effect level (NOEL).

Suspected endocrine disrupting substances

“…A two-generation study with rats exposed to resorcinol by drinking water was conducted by Welsch et al (2008). Although not stated in the original article, but in the review by Welsch (2008) this two-generation study was in accordance with OECD TG 416.…”

“…Besides the study by Welsch et al in 2008, the here reviewed publications on resorcinol exposure to rodents, were all performed long before the development of the OECD GD 150. For the sake of comparison they can all be regarded as repeated dose studies similar to the TG 407 or TG 408.…”

“…In contradiction to this, no effects on thyroid hormone levels or other significant thyroid histological effects were observed in a study where rats received resorcinol by gavage in concentrations ranging from 32 to 520 mg/kg/bw/d (NTP 1992). Welsch et al (2008) performed a study according to TG 416 where the maximum daily dose for F0 and F1 rats were 233 mg/bw/d in males, 304 mg/bw/d in premating/gestation females and 660 mg/bw/d in lactating females. It was concluded that males were more susceptible and histopathological effects on thyroid gland caused by resorcinol were confirmed in F0 males.…”

Voltammetric Study and Rapid Quantification of Resorcinol in Hair Dye and Biological Samples Using Ultrasensitive Maghemite/MWCNT Modified Carbon Paste Electrode

“…This has lead to significant amount of RS being emitted into environment, especially as waste effluents from many industries . Meanwhile, RS has been routinely used in hair dying applications and low levels of RS is also incorporated as an ingredient in pharmaceutical creams to treat ulcerating skin lesions, psoriasis, eczema, acne and as an eye drop . Despite the widespread applications, several evidences have classified RS as a threat to endocrine system .…”

A transcriptomics study on hepatic lipid metabolism in mice exposed to contaminated drinking water

“…Recently, drinking water safety has received great concern, since growing evidence indicates that long-term exposure to contaminated drinking water can induce carcinogenicity (Keshavarzi et al 2012), genotoxicity (Rebola et al 2011), and developmental (Kozul-Horvath et al 2012) and reproductive toxicities (Welsch et al 2008). Yangtze River is the longest river in China, and the river basin supports one-third of China's population and contributes about 40 % of the national gross domestic product of China ).…”